Search

Background: The establishment of apicobasal polarity in epithelial cells is of critical importance in morphogenesis of mammary gland and other secretive gland tissues. The demise of the polarity is a critical step in early stages of tumorigenesis such as in breast ductal carcinoma in situ. The underlying molecular mechanism thus warrants in-depth investigations. Results: Protein kinase C isoform ζ (PKCζ), which is highly expressed in breast cancer cells, accumulates in the nuclei of human mammary epithelial cells overexpressing human rhomboid family-1 (RHBDF1), an endoplasmic reticulum membrane protein. Nuclear translocation of PKCζ results in the failure of the formation of the cytosolic apicobasal polarity complex Par, of which PKCζ is an essential component. Additionally, enhanced nuclear translocation of PKCζ is accompanied by an inhibition of the expression of cell tight junction and adherens junction proteins and an increase of cell mobility. Mechanistically, RHBDF1 is able to interact with importin β1 and PKCζ and promote PKCζ phosphorylation. Consistently, treatment of RHBDF1-overexpressing cells with an inhibitor of PKCζ phosphorylation leads to restoration of apicobasal polarity and cell-cell junctions, as well as suppressed cell mobility. Conclusions: RHBDF1-facilitated nuclear translocation of PKCζ is critically responsible for the dismantlement of epithelial cell apicobasal polarity, and thus may serve as a target in the development of therapeutic approaches against early stages of breast cancer. [ABSTRACT FROM AUTHOR]

Introduction: Gastric cancer (GC) is an aggressive and heterogeneous malignancy marked by cellular and molecular diversity. In GC, cancer cells invade locally in the stomach at stage I and can progress to metastasis in distant organs by stage IV, where it often becomes fatal. Methods: We analyzed gene expression profiles from 719 stage I and stage IV GC patients across seven public datasets, conducting functional enrichment analysis to identify a gene signature linked to disease progression. Additionally, we developed an in vitro model of a simplified extracellular matrix (ECM) for cell-based assays. Results: Our analysis identified a progression-associated gene signature (APOD, COL1A2, FSTL1, GEM, LUM, and SPARC) that characterizes stage IV GC. This signature is associated with ECM organization and epithelial-to-mesenchymal transition (EMT), both of which influence the tumor microenvironment by promoting cell invasion and triggering EMT. Discussion: This gene signature may help identify stage I GC patients at higher risk, offering potential utility in early-stage patient management. Furthermore, our experimental ECM model may serve as a platform for investigating molecular mechanisms underlying metastatic spread in gastric cancer. [ABSTRACT FROM AUTHOR]

Objective To observe the regulatory effects of long non-coding RNA (lncRNA) JPX on the proliferation and invasion of nasopharyngeal carcinoma cells and to explore their mechanism. Methods The nasopharyngeal carcinoma cell lines CNE-1, 5-8F, 6-10B, HONE-1, C666-1 and nasopharyngeal normal epithelial cell line NP69 were selected, and we used RT-qPCR to detect the expression of lncRNA JPX in the cells. C666-1 cells with the highest expression of lncRNA JPX were taken as the study cells. C666-1 cells were randomly divided into the JPX down-expression group, down-expression control group, high JPX expression group, and high expression control group, respectively. They were transfected with JPX silencing sequence sh JPX, negative control sequence sh NC, JPX over-expression plasmid pcDNA3. 1- JPX, and negative control plasmid pcDNA 3. 1-NC, respectively. MTT assay was used to observe cell proliferation ability, and Trans well assay was used to observe cell invasion ability. We used the Star Base database to predict the targeted miRNAs and genes of lncRNA JPX, and found that lncRNA JPX had a targeted binding site with miR-1265, and miR-1265 had a targeted binding site with MAT1; the dual luciferase assay was used to verify the targeted relationship, and it showed that lncRNA JPX could bind to miR-1265 and inhibit miR-1265 expression, and miR-1265 could bind to MAT1 and inhibit MAT1 expression. Further, C666-1 cells were randomly divided into the control group, JPX down-regulation group, JPX down-regulation+miR-1265 down-regulation group, and JPX down-regulation+MAT1 down-regulation group, and were transfected with NC control sequence, sh JPX sequence, sh JPX+miR-1265 inhibitor sequence, and sh JPX+si-MAT1 sequence, respectively. Western blotting was used to detect the expression of MAT1 protein in cells of each group, MTT assay was used to observe cell proliferation ability, and Transwell assay was used to observe cell invasion ability. Results Cell viability and the number of invasive cells were as follows: the high JPX expression group > the high expression control group, and down-expression control group > JPX down-expression group (all P<0. 05) . The MAT1 protein expression, cell viability, the number of invasive cells were as follows: control group, JPX down-regulation+miR-1265 downregulation group > JPX down-regulation group > JPX down-regulation+MAT1 down-regulation group (all P<0. 05) . Conclusion LncRNA JPX can promote the proliferation and invasion of nasopharyngeal carcinoma cells, and its mechanism may be related to targeted regulation of the miR-1265/MAT1 axis. [ABSTRACT FROM AUTHOR]

Objective To observe the changes in invasion and migration abilities of lung adenocarcinoma cells with down-regulated histone acetyltransferase Tip60 and to investigate their underlying mechanisms. Methods The lung adenocarcinoma cell line A549 was divided into the Tip60 down-regulation group, negative control for down-regulation group, and control group. Cells in the Tip60 down-regulation group and the negative control for down-regulation group were transfected with Tip60-specific interfering siRNA and negative control siRNA, respectively, while cells in the control group were not transfected. The SETDB1 protein level in cells was detected using Western blotting, and the SETDB1 mRNA level was measured by real-time fluorescent quantitative PCR. Cell proliferation was assessed using the CCK-8 assay, cell invasion capability was evaluated using the Transwell chamber assay, and cell migration ability was observed using the wound healing assay. The significant enrichment peaks of histone H3 lysine 9 (H3K9) and lysine 27 (H3K27) were identified in the promoter region of SETDB1 in A549 lung adenocarcinoma cells by using the UCSC Browser feature of the Cistrome DB database. Chromatin immunoprecipitation (ChIP) was then performed to detect the acetylation levels of H3K9 and H3K27 in the promoter region of the SETDB1 gene. Results The expression levels of SETDB1 protein and mRNA in the Tip60 down-regulation group were lower than those in the control group and the negative control for down-regulation group (all P<0. 05) . At 24, 48, and 72 h of culture, the cell proliferation ability of the Tip60 down-regulation group was lower than those of the control group and the negative control for down-regulation group. The number of invasive cells was smaller in the Tip60 down-regulation group than in the control group and the negative control for down-regulation group. At 24 and 48 h of culture, the wound healing rate of the Tip60 down-regulation group was lower than those in the control group and the negative control for down-regulation group (all P<0. 05) . The acetylation levels of histone H3K9 and H3K27 in the SETDB1 promoter region were lower in the Tip60 down-regulation group than in the control group and the negative control for down-regulation group (all P<0. 05) . Conclusion Down-regulation of Tip60 can inhibit the invasion and migration abilities of lung adenocarcinoma cells, and the mechanism may be related to the regulation of acetylation levels of histone H3 in the SETDB1 promoter region. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of long non-coding RNA (lncRNA) GIHCG targeting microRNA (miR)-429 on the proliferation, migration, and invasion of esophageal squamous cell carcinoma (ESCC) cells. Meth⁃ ods Human ESCC cell lines (EC9706, TE1, and KYSE150 cells) and normal esophageal squamous epithelial cell line (Het-1A cells) were routinely cultured. The expression levels of lncRNA GIHCG and miR-429 in the cells were detected by RT-PCR, and the experimental cells were screened. The experimental cells in the logarithmic growth phase were randomly divided into the si-NC group and the si-GIHCG group, which were transfected with lncRNA knockdown plasmid negative control and lncRNA GIHCG knockdown plasmid, respectively. The expression levels of lncRNA GIHCG and miR429 in cells were detected by RT-PCR. The proliferation ability of the cells [optical density (OD) value] was detected by CCK-8. The migration ability of the cells was detected by cell scratch test. The invasion ability of the cells was detected by Transwell chamber test. The expression levels of cell proliferation phenotype proteins [CyclinD1, proliferating cell nuclear antigen (PCNA)] and metastasis phenotype proteins [matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9)] in the cells were detected by Western blotting. The experimental cells in the logarithmic growth phase were randomly divided into the GIHCG-WT + miR-429 mimics group, the GIHCG-WT + NC-mimics group, the GIHCG-MUT + miR-429 mimics group, and the GIHCG-MUT + NC-mimics group, respectively. The targeted relationship between lncRNA GIHCG and miR-429 was verified by dual luciferase reporter gene assay. Results Compared with Het-1A cells, the relative expression levels of lncRNA GIHCG in EC9706, TE1 and KYSE150 were higher (all P<0. 05), and the relative expression levels of miR-429 were lower (all P<0. 05). Since the relative expression level of lncRNA GIHCG was the highest and the relative expression level of miR-429 was the lowest in TE1 cells, TE1 cells were used as the experimental cells. Compared with the si-NC group, the relative expression level of lncRNA GIHCG in the si-GIHCG group was lower, the relative expression level of miR-429 was higher, the OD values were lower, the percentage of cell movement distance was lower, and the relative expression levels of CyclinD1, PCNA, MMP-2 and MMP-9 were lower, and the differences were statistically significant (all P<0. 05). Compared with the GIHCG-WT + NC-mimics group, the relative luciferase activity in the GIHCG-WT + miR-429 mimics group was lower (P<0. 05); there was no statistically significant difference in the relative luciferase activity between the GIHCG-MUT + miR-429 mimics group and the GIHCG-MUT + NC-mimics group (P> 0. 05). Conclusions The lncRNA GIHCG is highly expressed and the miR-429 is low expressed in ESCC cells. Knockdown of lncRNA GIHCG inhibits the proliferation, migration and invasion of ESCC cells by targeting miR-429. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti‐apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement. [ABSTRACT FROM AUTHOR]

Serine-threonine kinase receptor-associated protein (STRAP) regulates cell proliferation and apoptosis by binding to many target proteins and plays an important regulatory role in tumor development. We studied the effects of STRAP on non-small cell lung cancer (NSCLC) in vivo and in vitro in order to elucidate possible mechanisms underlying the regulatory effects of this protein. The levels of STRAP in NSCLC tissues and cells were determined by quantitative reverse transcription PCR, immunohistochemical staining, and Western blotting. In in vitro experiments, A549 and HCC827 cells were transfected with small interfering RNA (siRNA) to knockdown STRAP (si-STRAP) or with negative control sequence; cell migration and invasion were detected by scratch and Transwell assays, respectively. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), caspase-3, and caspase-9 were determined by Western blotting. In addition, we analyzed changes of tumor volume in a nude mouse NSCLC model. STRAP was highly expressed in NSCLC tissues and cells, but its expression was significantly suppressed in A549 and HCC827 cells transfected with si-STRAP. STRAP knockdown resulted in a significant inhibition of migration and invasion of A549 and HCC827 cells. It also significantly reduced the expression of XIAP and elevated expression of caspase-3 and caspase-9. In nude mice with tumor originated from transplanted A549 cells, inhibition of STRAP expression retarded the tumor growth. Overall, these findings indicate that STRAP is overexpressed in NSCLC, while knockdown of STRAP gene inhibits the growth of NSCLC. [ABSTRACT FROM AUTHOR]

Gliomas represent the most common primary Central Nervous System (CNS) tumors, characterized by increased heterogeneity, dysregulated intracellular signaling, extremely invasive properties, and a dismal prognosis. They are generally resistant to existing therapies and only a few molecular targeting options are currently available. In search of signal transduction pathways with a potential impact in glioma growth and immunotherapy, the Slit guidance ligands (Slits) and their Roundabout (Robo) family of receptors have been revealed as key regulators of tumor cells and their microenvironment. Recent evidence indicates the implication of the Slit/Robo signaling pathway in inflammation, cell migration, angiogenesis, and immune cell infiltration of gliomas, suppressing or promoting the expression of pivotal proteins, such as cell adhesion molecules, matrix metalloproteinases, interleukins, angiogenic growth factors, and immune checkpoints. Herein, we discuss recent data on the significant implication of the Slit/Robo signaling pathway in glioma pathology along with the respective targeting options, including immunotherapy, monoclonal antibody therapy, and protein expression modifiers. [ABSTRACT FROM AUTHOR]

Mdmx (Mdm4) is established as an oncogene mainly through repression of the p53 tumour suppressor. On the other hand, anti-oncogenic functions for Mdmx have also been proposed, but the underlying regulatory pathways remain unknown. Investigations into the effect of inhibitors for the NEDD8 pathway in p53 activation, human cell morphology, and in cell motility during gastrulation in Xenopus embryos revealed an anti-invasive function of Mdmx. Through stabilisation and activation of the RhoA GTPase, Mdmx is required for the anti-invasive effects of NEDDylation inhibitors. Mechanistically, through its Zn finger domain, Mdmx preferentially interacts with the inactive GDP-form of RhoA. This protects RhoA from degradation and allows for RhoA targeting to the plasma membrane for its subsequent activation. The effect is transient, as prolonged NEDDylation inhibition targets Mdmx for degradation, which subsequently leads to RhoA destabilisation. Surprisingly, Mdmx degradation requires non-NEDDylated (inactive) Culin4A and the Mdm2 E3-ligase. This study reveals that Mdmx can control cell invasion through RhoA stabilisation/activation, which is potentially linked to the reported anti-oncogenic functions of Mdmx. As inhibitors of the NEDD8 pathway are in clinical trials, the status of Mdmx may be a critical determinant for the anti-tumour effects of these inhibitors. [ABSTRACT FROM AUTHOR]

Background: Hilar cholangiocarcinoma (HCCA) is a common type of cholangiocarcinoma (CHOL) that originates from the right and/or left hepatic duct near the biliary tract confluence. The objective of this study is to investigate the impact of miR-182-5p on the proliferation and invasion of HCCA cells and identify a potential target for HCCA treatment. Methods: HCCA tissues were collected and HCCA cells were cultured. miR-182-5p and F-box and WD repeat domain containing 7 (FBXW7) were detected. After transfection of miR-182-5p inhibitor into HCCA cells, cell proliferation and invasion were detected by cell counting 8-kit and Transwell assay. FBXW7 expression was detected by Western blot. The targeted relationship between miR-182-5p and FBXW7 3’UTR was verified by dual-luciferase report assay. si-FBXW7 and miR-182-5p inhibitor were transfected into cells for combined experiments. HCCA cells with lowly-expressed miR-182-5p were injected into nude mice to establish the xenograft tumor model, and subsequent observations were made on tumor growth and gene expression changes. Results: miR-182-5p exhibited high expression levels in both HCCA tissues and cell lines. Inhibiting miR-182-5p effectively suppressed the proliferation and migration of HCCA cells. miR-182-5p bounded to FBXW7 3 ‘UTR and inhibited FBWX7 expression. Suppressing FBXW7 expression partially reversed the inhibitory effect of miR-182-5p inhibitor on HCCA cell proliferation and invasion. Silencing miR-182-5p could inhibit the HCCA growth in vivo. Conclusion: miR-182-5p promoted the proliferation and invasion of HCCA cells by targeting and inhibiting FBXW7 expression. [ABSTRACT FROM AUTHOR]

Glioma, a formidable form of brain cancer, poses significant challenges in terms of treatment and prognosis. Circular RNA nucleoporin 98 (circNUP98) has emerged as a potential regulator in various cancers, yet its role in glioma remains unclear. Here, we elucidate the functional role of circNUP98 in glioma cell proliferation, invasion, and migration, shedding light on its therapeutic implications. Glioma cells were subjected to si‐NUP98 transfection, followed by assessments of cell viability, proliferation, invasion, and migration. Subcellular localization of circNUP98 was determined, and its downstream targets were identified. We delineated the binding relationships between circNUP98 and microRNA (miR)‐520f‐3p, as well as between miR‐520f‐3p and ETS transcription factor ELK4 (ELK4). The expression levels of circNUP98/miR‐520f‐3p/ELK4 were quantified. Our findings demonstrated that circNUP98 was upregulated in glioma cells, and its inhibition significantly attenuated glioma cell proliferation, invasion, and migration. Mechanistically, circNUP98 functioned as a sponge for miR‐520f‐3p, thereby relieving the inhibitory effect of miR‐520f‐3p on ELK4. Moreover, inhibition of miR‐520f‐3p or overexpression of ELK4 partially rescued the suppressive effect of circNUP98 knockdown on glioma cell behaviors. In summary, our study unveils that circNUP98 promotes glioma cell progression via the miR‐520f‐3p/ELK4 axis, offering novel insights into the therapeutic targeting of circNUP98 in glioma treatment. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to compare the effects of the molecular targeted drugs, sorafenib and lenvatinib, on the survival, invasion, and angiogenesis of hepatocellular carcinoma cells. Additionally, we investigated the involvement of transforming growth factor beta (TGF‐β) signaling in their molecular mechanisms. Methods: To investigate the effects of sorafenib and lenvatinib, we conducted cell viability, invasion, and angiogenesis assays, as well as western blotting analyses. Results: In human hepatocellular carcinoma cells (HepG2), sorafenib demonstrated potent inhibitory effects on cell proliferation, but induced cell invasion similar to TGF‐β. In contrast, lenvatinib showed weaker cytotoxicity compared with sorafenib, but suppressed cell invasion induced by TGF‐β. The actions of these two molecular targeted drugs were suggested to involve the regulation of the TGFβR2/ERK pathway. Moreover, in human umbilical vein endothelial cells, Sorafenib showed weaker cytotoxicity and enhanced the effects of TGF‐β on angiogenesis. Conversely, lenvatinib showed potent cytotoxic abilities and suppressed angiogenesis induced by TGF‐β. The actions of these two molecular targeted drugs were suggested to involve the regulation of the crosstalk between TGF‐β signaling and vascular endothelial growth factor signaling. Conclusions: Our findings indicate that both sorafenib and lenvatinib possess anticancer abilities by inducing the cytotoxicity of hepatocellular carcinoma cells. Furthermore, they show opposing effects on TGF‐β‐induced cell invasion and angiogenesis, thereby enhancing the understanding of the multifaceted functions of molecular targeted drugs in treating hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Bone defects caused by surgical interventions and the challenges of tumor recurrence and metastasis due to residual cancer cells significantly complicate the treatment of osteosarcoma (OS). To address these complex clinical challenges, we propose an innovative therapeutic strategy that centers on an ultrasound-activated multifunctional bioactive calcium phosphate (BioCaP) composite. A modified curcumin (mcur)-mediated wet biomimetic mineralization process was used to develop an anticancer-drug-integrated multifunctional BioCaP (mcur@BioCaP), exploring its potential biological effects for OS treatment activated by ultrasound (US). The mcur@BioCaP demonstrates a drug dose-dependent, tailorable alteration in its micro/nanostructure. The US stimulus significantly enhanced this composite to generate reactive oxygen species (ROS) in cancer cells. The results show that the OS cell viability of the mcur@BioCaP with US is 62.2% ± 6.3%, the migration distance is 63.9% ± 6.6%, and the invaded OS cell number is only 57.0 ± 3.7 OS cells per version, which were all significantly lower than US or mcur@BioCaP alone, suggesting that the anticancer, anti-migratory and anti-invasive effects of mcur@BioCaP on OS 143B cells were amplified by ultrasonic stimulation. This amplification can be attributed to the US-activated ROS production from the drug molecules, which regulates the wet biomimetic mineralization of the multifunctional composite. Furthermore, mcur@BioCaP with US increased calcium nodule formation by 1.8-fold, which was significantly higher than mcur@BioCaP or US group, indicating its potential in promoting bone regeneration. The anticancer and osteogenic potentials of mcur@BioCaP were found to be consistent with the mcur concentration in the multifunctional composite. Our research provides a novel therapeutic approach that leverages a multifunctional biomimetic mineral and ultrasonic activation, highlighting its potential applications in OS therapy. [ABSTRACT FROM AUTHOR]

Objective To analyze the targeted relationship between miR-146a-5p and SMAD4 by observing the expression changes of microRNA-146a-5p (miR-146a-5p)and SMAD4 homolog 4（SMAD4)in follicular thyroid carcinoma (FTC)tissues and their effects on cell proliferation migration and invasion abilities, in order to explore whether miR-146a5p promotes invasion and metastasis of FTC by targeting SMAD4. Methods We collected 30 samples of FTC tissues and 30 samples of non-tumor thyroid tissues or tissues adjacent to the tumor margin (>2 cm)from patients with FTC. We used RT-qPCR to detect miR-146a-5p and SMAD4 mRNA in the FTC tissues and adjacent tissues. The FTC-238 cells were di‐ vided into the miR-146a-5p mimics group and the negative control (miR-NC group), which were transfected with miR146a-5p mimics (to overexpress miR-146a-5p in the cells)and miR-NC, respectively. CCK-8 was used to observe the cell proliferation abilities of the two groups at 12，24, and 48 h of culture. The scratch test was used to observe the migration abilities of the two groups, and the Transwell chamber experiment was used to observe the invasion abilities of the two groups. RT-qPCR and Western blotting were used to detect SMAD4 mRNA and protein in the two groups, respectively. The dual luciferase reporter gene experiment was used to verify the targeted relationship between miR-146a-5p and SMAD4. Results The relative expression level of miR-146a-5p in FTC tissues was lower than that in the adjacent tissues (P<0. 05). The relative expression level of SMAD4 mRNA in FTC tissues was higher than that in adjacent tissues (P< 0. 05). The OD value at each time point in the miR-146a-5p mimics group was lower than that in the miR-NC group (all P< 0. 05). The number of migration and invasive cells after transfection in the miR-NC group was larger than that in the miR146a mimics group (P<0. 05). The relative expression levels of SMAD4 mRNA and protein in the miR-146a-5p mimics group were lower than those in the miR-NC group (both P<0. 05). There was a targeted relationship between miR-146a-5p and SMAD4. Conclusion In FTC tissues, the expression of miR-146a-5p decreases while the expression of SMAD4 increases. Overexpression of miR-146a-5p can inhibit the proliferation, migration, and invasion of the FTC-238 cells. There is a targeted relationship between miR-146a-5p and SMAD4. MiR-146a-5p may promote the proliferation, invasion, and migration of FTC cells by targetedly inhibiting SMAD4. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of trigonelline (TRG) on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC) cells by regulating hypoxia inducible factor-la (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway. Methods: (1) In vitro experiments: NSCLC cell lines (A549) were randomly divided into control group (Control group, normal culture), TRG low concentration group (TRG-Low group, 25 μΜ), TRG high concentration group (TRG-High group, 50 µM), TRG high concentration+HIF-la activator dimethyloxalylglycine group (TRG-High+DMOG group, 50 μ.Μ TRG+10 µM DMOG). The proliferation, migration and invasion abilities of cells in each group were detected by Cell Counting Kit-8 (CCK-8) method, cell scratch assay, and transfer the chamber (Transwell), respectively. (2) In vivo experiment: 60 SPF male Rowett nude mice were randomly divided into normal group (NC group), in situ NSCLC model group (Model group), TRG low dose group (TRG-Low group, 40 mg/kg TRG), TRG high dose group (TRG-High group, 80 mg/kg TRG) and TRG high dose+DMOG group (TRG-High+DMOG group, 80 mg/kg TRG+40 mg/kg DMOG), TRG and DMOG were injected intraperitoneally, with 12 mice in each group. The lung tissue in each group of rats was taken for lung weight index and total tumor load measurement at the end of the experiment. The pathological changes of lung in each group were observed by hematoxylin-cosin (HE) staining. The apoptosis rate in lung tissue was evaluated by in situ end labeling (TUNEL) assay. The expression of HIF-1α, VEGF, cyclin D1 (cyclinD1), E-cadherin (E-cadherin) and vimentin (Vimentin) in lung tissue of rats in each group were detected by immunoblot experiments (Western Blot). Results: (1) In vitro experiments: The survival rate, cell migration rate and cell invasion number of A549 cells in TRG-Low group and TRG-High group were significantly lower than those in control group (P<0.05). The survival rate, cell migration rate and cell invasion number of A549 cells in TRG-High+DMOG group were significantly higher than those in TRG-High group(P<0.05). (2) In vivo experiment: The lung weight index, total tumor load, HIF-1α, VEGF, CyclinD1 and Vimentin protein expression in Model group were significantly higher than those in NC group (P<0.05), and the apoptosis rate and E-cadherin protein expression were significantly decreased (P<0.05). The pathological damage of lung tissue was serious, and there were obvious NSCLC lesions. The lung weight index, total tumor load, HIF-1α, VEGF, CyclinD1 and Vimentin protein expression in TRG-High group were significantly lower than thoes in Model group(P<0.05), the apoptosis rate and E-cadherin protein expression level were significantly higher than those in Model group (P<0.05), the pathological damage of lung tissue was reduced, and the NSCLC lesions were reduced. DMOG alleviated the inhibitory effect of TRG on NSCLC (P<0.05). Conclusion: TRG may inhibit the proliferation, migration and invasion of NSCLC cells by inhibiting the HIF-1α/VEGF signaling pathway in vitro and in vivo to prevent progression of NSCLC. [ABSTRACT FROM AUTHOR]

Glial-cell-line-derived neurotrophic factor (GDNF) is highly expressed and is involved in the malignant phenotype in glioblastomas (GBMs). However, uncovering its underlying mechanism for promoting GBM progression is still a challenging work. In this study, we found that serine protease inhibitor family E member 1 (SERPINE1) was a potential downstream gene of GDNF. Further experiments confirmed that SERPINE1 was highly expressed in GBM tissues and cells, and its levels of expression and secretion were enhanced by exogenous GDNF. SERPINE1 knockdown inhibited the migration and invasion of GBM cells promoted by GDNF. Mechanistically, GDNF increased SERPINE1 by promoting the phosphorylation of SMAD2/3. In vivo experiments demonstrated that GDNF facilitated GBM growth and the expressions of proteins related to migration and invasion via SERPINE1. Collectively, our findings revealed that GDNF upregulated SERPINE1 via the SMAD2/3-signaling pathway, thereby accelerating GBM cell migration and invasion. The present work presents a new mechanism of GDNF, supporting GBM development. [ABSTRACT FROM AUTHOR]

Aberrant N-glycosylation has been associated with progression of the pediatric cancer neuroblastoma (NB) but remains understudied. Here we investigated oligomannose N-glycans in NB by genetic editing of MGAT1 in a human NB cell line, BE(2)-C, called BE(2)-C(MGAT1−/−). Lectin binding studies confirmed that BE(2)-C(MGAT1−/−) had decreased complex and increased oligomannose N-glycans. The relevance of 2D and 3D cell cultures was demonstrated for cell morphology, cell proliferation, and cell invasion, thereby highlighting the necessity for 3D cell culture in investigating cancerous properties. Western blotting revealed that oligomannosylated EGFR had increased autophosphorylation. Proliferation was decreased in BE(2)-C(MGAT1−/−) using 2D and 3D cultures, but both cell lines had similar proliferation rates using 3D cultures without serum. Upon EGF treatment, BE(2)-C(MGAT1−/−), but not BE(2)-C, showed increased proliferation, and furthermore, the mutant proliferated much faster than BE(2)-C under 3D conditions. Cell spheroid invasiveness was greatly increased in BE(2)-C(MGAT1−/−) compared with BE(2)-C. Moreover, invasiveness was reduced in both cell lines with either EGF or RhoA activator treatment, regardless of the N-glycan population. Thus, this study further extends our earlier findings that oligomannose N-glycans enhance NB cell invasiveness, and that EGF stimulation of oligomannosylated EGFR greatly enhances cell proliferation rates, underlining the role of oligomannose N-glycans in the promotion of NB. [ABSTRACT FROM AUTHOR]

Simple Summary: The effects of magnetic fields on health and disease have been subject to considerable research interest for the past few decades but still remain relatively poorly understood. Therefore, the identification of molecular and cellular pathways affected is of considerable importance. This study investigated the effects of very low magnetic field (LMF) exposure in a cellular model of prostate cancer (PCa), the second most common cancer diagnosed in men. Extracellular vesicles (EVs) are lipid structures released from and taken up by cells and play crucial roles in cell communication and in processes such as cancer spread via their protein and nucleic acid cargoes. Short-term (4 h) LMF exposure significantly altered the release profiles and protein content of EVs from PCa cells to a more pro-cancerous profile. We then investigated changes in several key micro-RNAs, which are regulators of cancer behaviour and indicators of cancer aggressiveness and metastasis. LMF exposure caused significant upregulation of three key oncogenic miRNAs (miR-155, miR-21, and miR-210) and significant downregulation of two key tumour-suppressive miRNAs (miR-126 and miR-200c) in the PCa cells. These changes were also associated with a significant increase in the cancer cells' invasion capability, which is a key indicator of cancer aggressiveness. We further verified the metastatic ability of the cancer cells caused by the LMF exposure by assessing two metastasis-related proteins, matrix metalloproteinases MMP2 and MMP9, which both were significantly increased. We compared these findings with normal prostate cells, which showed fewer changes in response to LMF exposure. Our findings suggest that LMF exposure may promote a more aggressive cancer phenotype by modulating key molecular and cellular pathways, highlighting the potential therapeutic implications of magnetic field modulation in cancer treatment. Prostate cancer is the second most common neoplasia and fifth-leading cause of cancer death in men worldwide. Electromagnetic and magnetic fields have been classified as possible human carcinogens, but current understanding of molecular and cellular pathways involved is very limited. Effects due to extremely low magnetic/hypomagnetic fields (LMF) are furthermore poorly understood. Extracellular vesicles (EVs) are crucial mediators of cellular communication with multifaceted roles in cancer progression, including via transport and uptake of various protein and microRNA (miRNA) EV-cargoes. miRNAs regulate gene expression and are implicated in cancer-related processes such as proliferation, metastasis, and chemoresistance. This study investigated the effects of LMF exposure (20 nT) by magnetic shielding on the prostate cancer cell line PC3 compared to the prostate epithelial cell line PNT2 under short-term (4 h) conditions. We examined EV profiles following a 4 h LMF exposure alongside associated functional enrichment KEGG and GO pathways for the EV proteomes. The 4 h LMF exposure significantly reduced cellular EV release and modified PC3 EV cargoes to a more inflammatory and metastatic profile, with 16 Disease Pathways and 95 Human Phenotypes associated specifically with the LMF-treated PC3 EV proteomes. These included cancerous, metabolic, blood, skin, cardiac and skeletal Disease Pathways, as well as pain and developmental disorders. In the normal PNT2 cells, less EV protein cargo was observed following LMF exposure compared with cells not exposed to LMF, and fewer associated functional enrichment pathways were identified. This pointed to some differences in various cellular functions, ageing, defence responses, oxidative stress, and disease phenotypes, including respiratory, digestive, immune, and developmental pathways. Furthermore, we analysed alterations in matrix metalloproteinases (MMPs) and miRNAs linked to metastasis, as this is crucial in cancer aggressiveness. The 4 h LMF exposure caused a significant increase in MMP2 and MMP9, as well as in onco-miRs miR-155, miR-210, miR-21, but a significant reduction in tumour-suppressor miRs (miR-200c and miR-126) in the metastatic PC3 cells, compared with normal PNT2 cells. In addition, 4 h LMF exposure significantly induced cellular invasion of PC3 cells. Overall, our findings suggest that changes in magnetic field exposures modulate EV-mediated and miR-regulatory processes in PCa metastasis, providing a basis for exploring novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Escherichia coli O157:H7 (E. coli O157) is known for causing severe foodborne illnesses such as hemorrhagic colitis and hemolytic uremic syndrome. Although E. coli O157 is typically regarded as an extracellular pathogen and a weak biofilm producer, some E. coli O157 strains, including a clinical strain ATCC 43895, exhibit a notable ability to invade bovine crypt cells and other epithelial cells, as well as to form robust biofilm. This invasive strain persists in the bovine host significantly longer than non-invasive strains. Various surface-associated factors, including lipopolysaccharides (LPS), flagella, and other adhesins, likely contribute to this enhanced invasiveness and biofilm formation. In this study, we constructed a series of LPS-core deletion mutations (waaI, waaG, waaF, and waaC) in E. coli O157 ATCC 43895, resulting in stepwise truncations of the LPS. This approach enabled us to investigate the effects on the biosynthesis of key surface factors, such as flagella and curli, and the ability of this invasive strain to invade host cells. We confirmed the LPS structure and found that all LPS-core mutants failed to form biofilms, highlighting the crucial role of core oligosaccharides in biofilm formation. Additionally, the LPS inner-core mutants ΔwaaF and ΔwaaC lost the ability to produce flagella and curli. Furthermore, these inner-core mutants exhibited a dramatic reduction in adherence to and invasion of epithelial cells (MAC-T), showing an approximately 100-fold decrease in cell invasion compared with the outer-core mutants (waaI and waaG) and the wild type. These findings underscore the critical role of LPS-core truncation in impairing flagella and curli biosynthesis, thereby reducing the invasion capability of E. coli O157 ATCC 43895. [ABSTRACT FROM AUTHOR]

Background: The incidence of oral squamous cell carcinoma (OSCC) is increasing, and more effective treatment protocols must rapidly be developed to prevent the death of patients and ensure favorable outcomes. CircRNAs are a unique class of noncoding ribonucleic acid (RNA) molecules unaffected by RNA exonucleases. CircRNAs have more stable expression than linear RNAs and are not readily degraded; therefore, they are the newest focus of RNA research. Here, we analyze the mechanism of hsa_circ_0004771 (circ_0004771) in OSCC to provide a clinical reference. Methods: Circ_0004771 expression was measured in peripheral blood, cancerous tissues and adjacent tissues of OSCC patients. Patients were followed up for 3 years. The diagnostic value of circ_0004771 for OSCC occurrence, prognosis, recurrence and survival was analyzed with receiver operating characteristic (ROC) curves. OSCC cells were lentivirally transduced with a circ_0004771‐silencing or an empty vector to evaluate alterations in cell growth, invasion, and apoptosis. Apoptosis‐related and epithelial–mesenchymal transition (EMT)‐related protein expression was quantified. BALB/c nude mice were used for tumorigenesis experiments to evaluate tumor growth in vivo after silencing circ_0004771. Results: Circ_0004771 expression was higher in peripheral blood and cancerous tissue of OSCC patients than in control peripheral blood and paracancerous tissue, respectively, exhibiting excellent predictive value for OSCC occurrence, prognosis, recurrence and survival. Silencing circ_0004771 decreased the growth, invasiveness, and EMT capacity and increased the apoptosis of OCC cells. In mice implanted with OSCC cells transduced with the circ_0004771‐silencing lentiviral vector, the tumor growth capacity was obviously decreased. Conclusion: Silencing circ_0004771 inhibits the malignant growth of OSCC. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Listeria monocytogenes is known as a potentially pathogen, which can cause perinatal listeriosis, results in abortion, stillbirth or premature birth. Different factors are involved in the pathogenesis, including internalin B, which mediates the internalization of bacteria into a broad range of cell lines. However, it is not clear if expression of this protein is the same between different isolates. Methods: This study was conducted with the aim to compare L. monocytogenes isolated from pregnant women (n= 7) with different pregnancy outcomes (including healthy birth, still birth or blindness) and with abortion (n= 1), regarding expression level of inlB (internalin B encoding gene) and cell invasion. Results: Despite overexpression of inlB in most of the isolates, there was heterogeneity in the expression level between different isolates and no significant association with cell invasion and/ or pregnancy outcome was found (P> 0.05). About half of the studied isolates were able to invade HepG2 cells, while invasion to HeLa cells (cervix carcinoma cell line) was found only in one isolate. However, the difference was not significant. Likewise, no meaningful association was found between cell invasion and pregnancy outcomes. Conclusion: The expression level of inlB and cell invasion, cannot explain the difference of isolates in pathogenicity. Further studies are needed to identify bacterial and possibly host determinants.

Lim Domain and Actin Binding protein1 (lima1) influence cancer cell function. Thus far, functional role of lima1 in cholangiocarcinoma remains unknown. We used public databases, in vitro experiments, and multi-omics analysis to investigate the Lima1 in cholangiocarcinoma. Our results showed that lima1 expression is significantly upregulated and high levels of lima1 are significantly associated with vascular invasion in cholangiocarcinoma. Furthermore, lima1 knocking out inhibits the RBE cell invasion. Multi-omics data suggest that lima1 affect a broad spectrum of cancer related pathways, promoting tumor progression and metastatic ability in cholangiocarcinoma. This study provides insights into molecular associations of lima1 with tumorigenesist and establishes a preliminary picture of the correlation network in cholangiocarcinoma.

Aberrant N-glycosylation has been associated with progression of the pediatric cancer neuroblastoma (NB) but remains understudied. Here we investigated oligomannose N-glycans in NB by genetic editing of MGAT1 in a human NB cell line, BE(2)-C, called BE(2)-C(MGAT1−/−). Lectin binding studies confirmed that BE(2)-C(MGAT1−/−) had decreased complex and increased oligomannose N-glycans. The relevance of 2D and 3D cell cultures was demonstrated for cell morphology, cell proliferation, and cell invasion, thereby highlighting the necessity for 3D cell culture in investigating cancerous properties. Western blotting revealed that oligomannosylated EGFR had increased autophosphorylation. Proliferation was decreased in BE(2)-C(MGAT1−/−) using 2D and 3D cultures, but both cell lines had similar proliferation rates using 3D cultures without serum. Upon EGF treatment, BE(2)-C(MGAT1−/−), but not BE(2)-C, showed increased proliferation, and furthermore, the mutant proliferated much faster than BE(2)-C under 3D conditions. Cell spheroid invasiveness was greatly increased in BE(2)-C(MGAT1−/−) compared with BE(2)-C. Moreover, invasiveness was reduced in both cell lines with either EGF or RhoA activator treatment, regardless of the N-glycan population. Thus, this study further extends our earlier findings that oligomannose N-glycans enhance NB cell invasiveness, and that EGF stimulation of oligomannosylated EGFR greatly enhances cell proliferation rates, underlining the role of oligomannose N-glycans in the promotion of NB.

Objective·To investigate the biological roles and associated mechanisms of the hypoxia-induced long non-coding RNA 68 (HILRNA68) in hepatocellular carcinoma (HCC) cell lines.Methods·Long non-coding RNA (lncRNA) microarray analysis was conducted to study the differential expression of lncRNAs in the HCC cell lines cultured under hypoxia treatment and normoxia treatment separately for 12 h, and DEseq2 R package was used for the analysis of differentially expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the differential lncRNAs. Short hairpin RNAs (shRNAs) were used to knock down hypoxia-inducible factors (HIFs) to investigate whether HILRNA68 transcription was regulated by HIFs under hypoxia. Nucleus-cytoplasmic isolation combined with qRT-PCR and RNA fluorescence in situ hybridization (RNA-FISH) experiments were used to investigate the subcellular localization of HILRNA68. HILRNA68 was knocked down in SMMC-7721 and MHCC-97H cells by small interfering RNA (siRNA) to investigate its cellular function under hypoxia. The impact of HILRNA68 on the cell proliferation and invasion capabilities of HCC cells under hypoxia was examined by cell counting and Transwell assays. Dual-luciferase reporter assay was employed to identify how HILRNA68 regulated the transcriptional activity of HIFs under hypoxia.Results·By differential expression analysis of lncRNAs, a total of 247 and 17 significantly (defined as fold change≥4, FDR≤0.05) up- and down-regulated lncRNAs, respectively, were identified. Among these differentially expressed genes, lncRNA HILRNA68 was up-regulated about 10-fold in multiple HCC cell lines when cultured under hypoxia for 12 h. Knockdown of HIF1α, HIF2α, and HIF1β significantly suppressed (all P

Abstract The role of cathepsin K (CTSK) expression in the pathogenesis and progression of gastric cancer (GC) remains unclear. Hence, the primary objective of this study is to elucidate the precise expression and biological role of CTSK in GC by employing a combination of bioinformatics analysis and in vitro experiments. Our findings indicated a significant upregulation of CTSK in GC. The bioinformatics analysis revealed that GC patients with a high level of CTSK expression exhibited enrichment of hallmark gene sets associated with angiogenesis, epithelial–mesenchymal transition (EMT), inflammatory response, KRAS signaling up, TNFα signaling via KFκB, IL2-STAT5 signaling, and IL6-JAK-STAT3 signaling. Additionally, these patients demonstrated elevated levels of M2-macrophage infiltration, which was also correlated with a poorer prognosis. The results of in vitro experiments provided confirmation that the over-expression of CTSK leads to an increase in the proliferative and invasive abilities of GC cells. However, further evaluation was necessary to determine the impact of CTSK on the migration capability of these cells. Our findings suggested that CTSK has the potential to facilitate the initiation and progression of GC by augmenting the invasive capacity of GC cells, engaging in tumor-associated EMT, and fostering the establishment of an immunosuppressive tumor microenvironment (TME).

Objective To investigate the expression of long non-coding RNA (lncRNA), surfactant associated 1 pseudogene (SFTA1P) in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines. Methods Based on the cancer genome atlas (TCGA) database, the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma. Then, the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction (RT-qPCR). SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids (pcDNA3.1-SFTA1P) and small interfering RNAs (si-SFTA1P-1 and si-SFTA1P-2). CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells. Differential gene expression analysis, correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells. Results Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue (P

Objective To discuss the role of ETS1 in development and progression of lung adenocarcinoma and to provide a theoretical basis for the screening of clinical biomarkers and targeted intervention for lung adenocarcinoma. Methods The UAlcan database was used to access the Cancer Genome Atlas (TCGA) database and the CPTAC database to compare the expression of ETSI in lung adenocarcinoma tissues and normal adjacent tissues. According to the expression of ETSI in lung adenocarcinoma tissues of the TCGA database, the overall survival (OS) of lung adenocarcinoma patients with high and low ETS1 expression was compared. Human lung adenocarcinoma A549 cells in the logarithmic growth phase were randomly divided into the si-NC group, si-ETS1 group, vector group and ETS1-OE group, which were transfected with si-NC, si-ETS1, peDNA3. 1 unloaded plasmid and peDNA3. 1-ETS1 overexpression plasmid by Lipofectamine™ 3000 transfection reagent, respectively. The relative expression of ETSI protein and mRNA was detected by Western blotting and real-time quantitative PCR, the cell proliferation ability (expressed by optical density value) was observed by CCK-8, the cell migration ability (expressed by scratch healing rate) was observed by cell scratch assay, and the cell invasion ability (expressed by the number of invasive cells) was observed by Transwell chamber assay. Results The results of TCGA and CPTAC database analysis showed that the expression of ETS1 in lung adenocarcinoma tissues was lower than that in the normal adjacent tissues (P<0.05). Compared with patients with low ETSI expression in lung adenocarcinoma, patients with high ETSI expression had longer OS (P<0.05). Compared with the si-NC group and the vector group, the relative expression levels of ETSI protein and mRNA in the si-ETS1 group decreased, and the relative expression levels of ETSI protein and mRNA in the ETS1-OE group increased (all P<0.05). Over the time of culture, the OD value of cells in each group showed an increasing trend. Compared with the si-NC group and the vector group at the same time point, the OD value of cells in the si-ETSI group increased, and the OD value of cells in the ETSI-OE group decreased (all P< 0.05). Compared with the si-NC group and the vector group at the same time point, the scratch healing rate and the number of invasive cells in the si-ETS1 group increased, and the scratch healing rate and the number of invasive cells in the ETS1-OE group decreased (all P<0.05). Conclusions ETSI expression in lung adenocarcinoma tissue decreases, which is associated with the prognosis of patients. The down-regulation of ETSI expression can accelerate the proliferation, migration and invasion of lung adenocarcinoma cells, suggesting its potential as a prognostic biomarker and therapeutic target gene for lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of miR-888-5p on the proliferation and invasion abilities of non-smallcell lung cancer (NSCLC) cells, and to explore the possible mechanism. Methods Real-time fluorescence quantitative PCR was used to detect the relative expression levels of miR-888-5p in NSCLC cell lines (A549, NCI-H1299, PC-9, LLC, and NCI-H1650) and human normal lung epithelial cell line (BEAS-2B), . A549 cells with the most significant changes in the miR-888-5p relative expression were selected for subsequent experiments. A549 cells were divided into the miR-888-5p mimics group, miR-888-5p inhibitor group, and scramble group, which were transfected with miR-888-5p mimics, miR-888-5p inhibitor, and scramble sequences, respectively. Real-time fluorescence quantitative PCR was used to detect the relative expression level of miR-888-5p in cells. MTT assay was used to detect the cell proliferation abilities at 0, 24, 48, and 72 h of culture. Transwell chamber invasion assay was used to detect the cell invasion ability (expressed as the number of invading cells), . StarBase online prediction website predicted that the target gene of miR-888-5p was Tob1, which was verified through luciferase assay. Western blotting was used to detect the relative expression levels of Tob1, E-cadherin, vimentin proteins, p-JAK2/JAK2, and p-STAT3/STAT3 in cells. Results The relative expression levels of miR-888-5p in the miR-888-5p mimics group, miR-888-5p inhibitor group, and scramble group were 48. 9 ± 1. 78, 1. 06 ± 0. 24, and 8. 23 ± 0. 90, respectively, with statistically significant difference between groups (all P<0. 05), . Over the time of culture, the proliferation abilities of the three groups showed an increasing trend. At the same time point, the cell proliferation abilities and the invasive cells decreased in the miR-888-5p mimics group, scramble group, and miR888-5p inhibitor group in turn, with statistically significant difference between groups (all P<0. 05), . The relative expression levels of Tob1 and E-cadherin proteins in the miR-888-5p mimics group, scramble group, and miR-888-5p inhibitor group increased sequentially, while the relative expression levels of vimentin protein and p-JAK2/JAK2, p-STAT3/STAT3 decreased sequentially (all P<0. 05), . Conclusion MiR-888-5p can enhance the proliferation and invasion abilities of NSCLC cells, and their mechanism may be related to the activation of JAK2/STAT signaling pathway and targeted downregulation of Tob1 expression, thereby promoting the epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

AIM: To explore the expression level of vitamin D receptor (VDR) in lung adenocarcinoma and its impact on the biological function of lung adenocarcinoma cells. METHODS: The mRNA expression level of VDR in lung adenocarcinoma and its relationship with prognosis were analyzed through 6 lung adenocarcinoma datasets (comprising a total of 792 lung adenocarcinoma tissues and 230 adjacent non-tumor tissues). Immunohistochemistry was used to detect VDR protein expression in 30 lung cancer patients. Lung adenocarcinoma cell lines A549 and H1650 were studied, with transfection of negative control (NC) or two VDR short hairpin RNAs (VDR-shRNAs). CCK-8 assay compared the cell viability of cells in each experimental group. Transwell and wound-healing assays compared the invasion and migration capabilities. Gene set enrichment analysis identified pathways enriched in lung adenocarcinoma tissues with high VDR expression. RESULTS: The mRNA expression level of VDR was significantly increased in lung adenocarcinoma tissues (P<0. 01). Immunohistochemistry further confirmed the high expression of VDR in lung adenocarcinoma (P< 0.01). The survival analysis showed that the expression of VDR had no significant effect on the overall survival of lung adenocarcinoma patients (P>0. 05). Knockdown of VDR significantly inhibited the cell viability, invasion, and migration ca⁃ pacity of lung adenocarcinoma cells (P<0. 05). Gene set enrichment analysis showed that lung adenocarcinoma tissues with high VDR expression were enriched in signaling pathways such as epithelial-mesenchymal transition (P<0. 05). CONCLUSION: VDR is highly expressed in lung adenocarcinoma, and VDR knockdown can inhibit the cell viability, invasion, and migration capacity of lung adenocarcinoma cells. [ABSTRACT FROM AUTHOR]

AIM: This study is aimed to investigate the impact of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) on the proliferation, invasion, and migration of human colorectal cancer (CRC) cell lines (SW480 and HCT116) and preliminarily explore the underlying molecular mechanisms. METHODS: Human colorectal cancer cells (SW480 and HCT116) cultured in vitro were subjected to various concentrations of HMF (0,12. 5,25 and 50 μmol/L) for 48 h. Proliferation levels were assessed using the CCK-8 assay, invasion abilities were examined via the Transwell assay, migra⁃ tion rates were measured using the scratch assay, and oxidative stress levels were determined by the DCF-DA reactive oxygenation assay. The mRNA expression levels of heme oxygenase-1 (HO-1) mRNA and NAD (P) H: quinone oxidoreductase-1 (NQO-1) were quantified using RT-qPCR. RESULTS: Treatment with varying concentrations of HMF resulted in a significant reduction in the proliferative capacity of SW480 and HCT116 cancer cells, as was indicated by CCK-8 experiments (P<0. 05). Transwell assays demonstrated a pronounced attenuation in the invasive potential of SW480 and HCT116 following HMF treatment (P<0. 05). Scratch assays highlighted a notable constraint on the migratory capabilities of SW480 and HCT116 after HMF treatment (P<0. 05). DCF-DA staining revealed a substantial increase in reactive oxygen species (ROS) levels within SW480 and HCT116 cells after HMF treatment (P<0. 05). Furthermore, RT-qPCR ex⁃ periments elucidated that HMF markedly suppressed the mRNA expression of antioxidant genes HO-1 and NQO-1. CONCLUSION: HMF induces oxidative stress response in SW480 and HCT116 cells, consequently inhibiting their proliferation, invasion and migration [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of a disintegrin and metalloproteinase (ADAM) domain-like decy-sin 1(ADAMDEC1) knockdown on the proliferation, migration and invasion of pancreatic carcinoma cells. METHODS: Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online databases. Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcinoma cell lines (MIA PaCa-2 and PANC-1) and pancreatic ductal cell line (hTERT-HPNE). The effects of ADAMDEC1 knockdown on cell proliferation, migration and invasion were evaluated using CCK-8, colony formation, wound-healing and Transwell assays. Additionally, Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers, as well as Wnt/β-catenin signaling pathway-related proteins in pancreatic carcinoma cells. Furthermore, a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling pathway agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migration. RESULTS:(1) ADAMDEC1 was highly expressed in pancreatic carcinoma cells. (2) Knockdown of ADAMDEC1 led to a significant reduction in the proliferation, migration and invasion of pancreatic carcinoma cells. (3) Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9, N-cadherin and vimentin proteins, alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related proteins. (4) Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation, migration, and invasion. CONCLUSION: ADAMDEC1 is highly expressed in pancreatic carcinoma. Targeted silencing of ADAMDEC1 has the potential to inhibit the proliferation, migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to study the correlation between preeclampsia (PE) and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and to examine the molecular mechanisms behind the development of PE. Methods: 30 PE and 30 normal pregnant women placental samples were assessed the levels of NEAT1 and miR-217 by quantitative real-time PCR (qRT-PCR). The trophoblast cell line HTR8/SVneo was used for silencing NEAT1 or miR-217 inhibitor in the absence or presence of an inhibitor and H2O2. Cell counting Kit 8 (CCK-8), flow cytometry, and Transwell were used to detect cell proliferation, apoptosis, migration, and invasion. Luciferase reporter gene assay was utilized to verify the binding between miR-217 and Wnt family member 3 (Wnt3), and between the miR-217 and NEAT1. Proteins related to the Wnt/β-catenin signaling pathway were detected using western blotting. Results: The PE group exhibited a significantly downregulated expression of miR-217 and a significantly upregulated expression of NEAT1. NEAT1 targeted miR-217, and Wnt is a miR-217 target gene. siRNA-NEAT1 inhibited the apoptosis of trophoblast cells, but promoted their invasion, migration, and proliferation. MiR-217 inhibitor could partially reverse the effects of siRNA-NEAT1. The expression of the Wnt/β-catenin signaling pathway-related proteins, WNT signaling pathway inhibitor 1 (DKK1), cyclin-D1 and β-catenin, was significantly increased after siRNA-NEAT1. Conclusions: NEAT1 could reduce trophoblast cell invasion and migration by suppressing miR-217/Wnt signaling pathway, leading to PE. [ABSTRACT FROM AUTHOR]

In eukaryotes, Hsp90B1 serves as a vital chaperonin, facilitating the accurate folding of proteins. Interestingly, Hsp90B1 exhibits contrasting roles in the development of various types of cancers, although the underlying reasons for this duality remain enigmatic. Through the utilization of the Drosophila model, this study unveils the functional significance of Gp93, the Drosophila ortholog of Hsp90B1, which hitherto had limited reported developmental functions. Employing the Drosophila cell invasion model, we elucidated the pivotal role of Gp93 in regulating cell invasion and modulating c‐Jun N‐terminal kinase (JNK) activation. Furthermore, our investigation highlights the involvement of the unfolded protein response‐associated IRE1/XBP1 pathway in governing Gp93 depletion‐induced, JNK‐dependent cell invasion. Collectively, these findings not only uncover a novel molecular function of Gp93 in Drosophila, but also underscore a significant consideration pertaining to the testing of Hsp90B1 inhibitors in cancer therapy. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM 2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM 2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM 2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5 µg/ml PM 2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM 2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM 2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM 2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2–5p, miR-3117–3p, miR-218–5p, and miR-497–5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM 2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM 2.5 -enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM 2.5 -triggered pathogenesis. • Exosomes from BEAS-2B cells chronically exposed to low-dose PM 2.5 promote the invasiveness of adjacent cells. • Exosomal miR-196b-5p may predict and trigger the malignant behavior of adjacent cells. • Exosomes harboring the miR-196b-5p inhibitor may suppress PM2.5-triggered pathogenesis. [ABSTRACT FROM AUTHOR]

This review focuses on the expression and function of voltage-gated sodium channel subtype NaV1.7 in various cancers and explores its impact on the metastasis driving cell functions such as proliferation, migration, and invasiveness. An overview of its structural characteristics, drug binding sites, inhibitors and their likely mechanisms of action are presented. Despite the lack of clarity on the precise mechanism by which NaV1.7 contributes to cancer progression and metastasis; many studies have suggested a connection between NaV1.7 and proteins involved in multiple signaling pathways such as PKA and EGF/EGFR-ERK1/2. Moreover, the functional activity of NaV1.7 appears to elevate the expression levels of MACC1 and NHE-1, which are controlled by p38 MAPK activity, HGF/c-MET signaling and c-Jun activity. This cascade potentially enhances the secretion of extracellular matrix proteases, such as MMPs which play critical roles in cell migration and invasion activities. Furthermore, the NaV1.7 activity may indirectly upregulate Rho GTPases Rac activity, which is critical for cytoskeleton reorganization, cell adhesion, and actin polymerization. The relationship between NaV1.7 and cancer progression has prompted researchers to investigate the therapeutic potential of targeting NaV1.7 using inhibitors. The positive outcome of such studies resulted in the discovery of several inhibitors with the ability to reduce cancer cell migration, invasion, and tumor growth underscoring the significance of NaV1.7 as a promising pharmacological target for attenuating cancer cell proliferation andmetastasis. The research findings summarized in this review suggest that the regulation of NaV1.7 expression and function by small molecules and/or by genetic engineering is a viable approach to discover novel therapeutics for the prevention and treatment of metastasis of cancerswith elevated NaV1.7 expression. [ABSTRACT FROM AUTHOR]

Objective To observe the regulatory effects of miR-381-3p on the proliferation, invasion, and migration abilities of oral cancer cells, and to explore the relevant mechanism based on methyltransferases SETDB1 gene regulation. Methods The miR-381-3p in the oral cancer cell line CAL-27 and the normal oral mucosal epithelial cell line ATCC was detected by RT-PCR. CAL-27 cells were cultured and divided into the mimic, negative control and untransfected groups, and cells in the mimic and negative control groups were transfected with miR-381-3p mimic and miR-381-3p negative control, respectively, and cells in the untransfected group were not transfected. cell proliferation ability was measured by CCK-8 assay, Transwell chamber assay was used to measure the cell invasion, and cell migration ability was determined by Scratch-healing assay. TargetScan（http：//www. targetscan. org/vert_80/) was used to predict the binding sites between miR-381-3p and SETDB1, and we tested this with the dual luciferase report gene analysis. The SETDB1 mRNA was detected by RT-PCR in CAL-27 cells and ATCC cells and SETDB1 protein was detected by Western blotting. CAL-27 cells were divided into the mimic group, negative control group and untransfected group, cells in the mimic and negative control groups were transfected with miR-381-3p mimic and miR-381-3p negative control, and cells in the untransfected group were not transfected. SETDB1 mRNA in each group was detected by RT-PCR. Results The expression of miR- 381-3p was lower in CAL-27 cells than in ATCC cells（ P<0. 05). The cell proliferation abilities of miR-381-3p in the mimic group were lower than those of the miR-381-3p negative control group and untransfected group at 12, 24, 36 and 48 h（all P<0. 05). The number of transmembrane cells and cell migration distance in miR-381-3p mimic group were lower than those in the miR-381-3p negative control group and untransfected group（all P<0. 05). SETB1 gene had a continuous nucleotide sequence that could complement miR-381-3p. Relative luciferase activity of CAL-27 cells co-transfected with SETDB1-WT and miR-381-3p was lower than that of cells in the other groups（all P<0. 05). The expression levels of SETDB1 mRNA and protein in the CAL-27 cells were higher than those in the ATCC cells（both P<0. 05)； the expression of SETDB1 mRNA was lower in the mimic group than in the negative control group and the untransfected group（all P<0. 05). Conclusion MiR-381-3p can inhibit the proliferation, invasion and migration of oral cancer cells, and its mechanism may be related to regulation of SETDB1 expression. [ABSTRACT FROM AUTHOR]

P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21-/-) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21-/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21-/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21-/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21-/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of microRNA-125a (miR-125a) on the proliferation, apoptosis, migration, invasion, and other biological behaviors of endometrial cancer (EC) cells and the mechanism. Methods Human EC cells (JEC, HEC-1B, and Ishikawa cells) and endometrial epithelial cells (ECS cells) were cultured routinely. The expression of miR-125a in cells was detected by RT-PCR, and the cells with the lowest expression of miR-125a were screened as experimental cells. EC cells in the logarithmic growth phase and with the lowest expression of miR-125a were taken and randomly divided into miR-NC group and miR-125a mimics group, which were transfected with miRNA negative control miR-NC and miR-125a mimics, respectively. The expression of miR-125a was detected by RT-PCR, the cell proliferation activity (OD value) was detected by CCK-8 assay, the cell colony formation ability was detected by plate cloning assay, the apoptosis ability (apoptosis rate) was detected by flow cytometry, the cell migration and invasion capacities were detected by Transwell chamber assay, and the intracellular LIN28B protein expression was detected by Western blotting. Results Compared with ECS cells, the relative expression levels of miR-125a in JEC, HEC-1B and Ishikawa cells were lower (all P<0. 05), and the relative expression of miR-125a in Ishikawa cells was the lowest, which were used as experimental cells. Compared with the miR-NC group, the expression of miR-125a in the miR-125a mimics group was higher (P <0. 05) . Compared with the miR-NC group, the OD values of miR-125a mimics group were lower after culture for 24, 48, and 72 h, and the number of colony formation was smaller, the apoptosis rate was higher, the migrating cells and invasive cells were less, and the relative expression of LIN28B protein was lower, and the differences were statistically significant (all P<0. 05) . Conclusion Up-regulation of miR-125a expression inhibits the proliferation, migration and invasion of EC cells and induces apoptosis, which may be related to its targeted regulation of LIN28B gene. [ABSTRACT FROM AUTHOR]

Objective: To discuss the expressions of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) in oral squamous cell carcinoma (OSCC) tissue and OSCC cells and its effect on the biological behavior of the OSCC cells, and to clarify the potential of PLOD1 as a prognostic biomarker for OSCC. Methods: The expression level of PLOD1 mRNA in head and neck squamous cell carcinoma (HNSC) tissue and its correlation with the survival of the HNSC patients were analyzed by Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier Plotter databases. Immunohistochemistry method was used to detect the expression level of PLOD1 protein in 110 OSCC tissue and 64 adjacent tissue, and its association with clinicopathological characteristics and prognosis of the OSCC patients were analyzed; the diagnostic value of PLOD1 in OSCC was detected by area under the curve (AUC) of the receiver operating characteristic (ROC). The expression levels of PLOD1 mRNA and protein in the human normal oral epithelial HOK cells and OSCC SCC15 and CAL27 cells were detected by real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting methods. The small interfering RNA (siRNA) fragments were transfected into the SCC15 cells by liposome method and the cells were dividing into si-NC group (transfected with negative control si-NC) and si-PLOD1 group (transfected with si-PLOD1); the proliferation activities, scratch healing rates, and numbers of invasion cells in two groups were detected by CCK-8 method, wound healing assay, and Transwell chamber assay, respectively. Results: The public database analysis results showed that the expression level of PLOD1 mRNA in HNSC tissue was higher than that in adjacent tissue(P<0. 05); compared with low expression of PLOD1 group, the survival period of the HNSC patients in high expression of PLOD1 group was shorter (HR=1. 41, P=0. 018). The PLOD1 protein was mainly expressed in cytoplasm of the OSCC cells, and the expression intensity of PLOD1 in OSCC tissue was higher than that in adjacent tissue (P<0. 01), and it was related to T stage and TNM stage of the OSCC patients (P=0. 021, P=0. 004). The AUC of PLOD1 for diagnosing OSCC was 0. 811, and the specificity was 63. 64% and the sensitivity was 90. 63%. The Kaplan-Meier survival analysis results showed that compared with low expression of PLOD1 group, the survival rate of the OSCC patients in high expression of PLOD1 group was decreased (P<0. 01). The COX regression analysis results showed that high expression of PLOD1 was an independent risk factor for the prognosis of OSCC (P=0. 012). The expression levels of PLOD1 mRNA and protein in the OSCC cells were higher than those in HOK cells (P<0. 05). Compared with si-NC group, the proliferation activity and scratch healing rate of the cells in si-PLOD1 group were decreased (P<0. 05), and the number of invasion cells was decreased(P< 0. 01). Conclusion: PLOD1 is highly expressed in the OSCC tissue and cells, and silencing of PLOD1 expression can inhibit the proliferation, migration, and invasion of the OSCC cells. PLOD1 may be a new therapeutic target and prognostic biomarker for OSCC. [ABSTRACT FROM AUTHOR]

Objective: To discuss the effect of sialic acid-binding immunoglobulin-like lectin-15(Siglec15) derived from M2 tumor-associated macrophages (M2-TAMs) on promoting the malignant biological behavior of the esophageal squamous cell carcinoma (ESCC) through bioinformatics analysis, and to validate the findings through cell experiment. Methods: The Tumor Immune Estimation Resource (TIMER) online Database was used to analyze the expression differences and immune infiltration of Siglec15 in pan-cancer and adjacent normal tissues. Real-time fluorescence quantitative PCR (RT-qPCR) method was used to detect the expression levels of Siglec15 mRNA in M2-TAMs and ESCC EC109 and KYSE150 cells. Based on the non-contact co-culture of M2-TAMs and ESCC cells, the following groups were set up，such as EC109/KYSE150 group, EC109/KYSE150+si-NC group (transfected with si-NC sequence), and EC109/KYSE150+si-Siglec15 group (transfected with si-Siglec15#1 and si-Siglec15#2 sequences). CCK-8 method was used to detect the proliferation activities of the cells in various groups; wound healing assay was used to detect the wound healing rates of the cells in various groups; Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups; flow cytometry was used to detect the apoptotic rates of the cells in various groups. Results: The bioinformatics analysis results showed that compared with adjacent normal tissue, the expression levels of Siglec15 mRNA in pan-cancer tissues such as esophageal cancer, colon cancer, and head and neck squamous cell carcinoma tissues were increased (P<0. 05 or P<0. 01), and the expression level of Siglec15 mRNA in esophageal cancer tissue was significantly positively correlated with the infiltration of the macrophages (P<0. 05). Compared with the EC109 cells and KYSE150 cells, the expression level of Siglec15 mRNA in M2-TAMs was significantly increased (P<0. 01). There was no significant difference in the proliferation rate of the cells among EC109/KYSE150 group, EC109/KYSE150+si-NC group, and EC109/KYSE150+si-Siglec15 group(P>0. 05). Compared with EC109/KYSE150 group, after treated for 24 and 48 h, the wound healing rate of the cells in EC109/KYSE150+si-NC group was increased (P<0. 01), the numbers of migration and invasion cells were increased (P<0. 05), and the apoptotic rate was decreased (P<0. 01). Compared with EC109/KYSE150+si-NC group, the wound healing rates of the cells in EC109/ KYSE150+si-Siglec15#1 group and EC109/KYSE150+si-Siglec15#2 group were decreased (P< 0. 05), the numbers of migration and invasion cells were decreased (P<0. 05), and the apoptotic rates of the cells had no significant difference (P>0. 05). Conclusion: Siglec15 derived from M2-TAMs may be a key factor in promoting the migration and invasion of the ESCC cells. [ABSTRACT FROM AUTHOR]

Transforming growth factor- β (TGF- β) is a multifunctional cytokine that plays a vital role in regulating cell growth, differentiation and survival in various tissues. It participates in a variety of cellular processes, including cell apoptosis, cell migration and evasion, and plays a paradoxical role in tumor genesis and development. In the early stage of tumor, TGF- β inhibits the occurrence of tumor by inhibiting cell proliferation and regulating cell apoptosis. In the advanced stage of tumor, TGF- β promotes tumor development and affects prognosis by promoting cell survival and proliferation, cell migration and invasion, participates in immune escape, etc. In this article, we will review the paradoxical role of TGF- β on the occurrence and development of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Objective To observe the changes in proliferation, migration, and invasion of human cervical cancer cell line HeLa with overexpression of microRNA-216a (miR-216a)/Calpain 6 (CAPN6) gene and their targeting relationships, and to explore the effects of miR-216a on the proliferation, migration, and invasion of HeLa cells. Methods HeLa cells in the logarithmic growth phase were divided into five groups: groups I, II, III, IV and V, with 6 well plates in each group. Cells in the group I were transfected with miR-216a mimic, cells in the group II were transfected with pcDNA3.1- CAPN6 plasmid, cells in the group III were sequentially transfected with miR-216a mimic and peDNA3.1-CAPN6, cells in the group IV were transfected with pcDNA3.1, and cells in the group V were transfected with miR-216a mimic NC. At 48 h of cultivation, the proliferation, migration, and invasion of cells in each group were observed by CCK-8 method, Scratch healing test and Transwell test. At 24 h of cultivation, miR-216a in each group was detected by qRT-PCR, and CAPN6 and signal transducer and activator of transcription 3 (STAT3) proteins in each group were detected by Western blotting. In addition, HeLa cells in the logarithmic growth phase were divided into four groups: cells in the group A were sequentially trans- fected with miR-216a mimic and pGL3-CAPN6-WT plasmids, cells in the group B were sequentially transfected with miR- 216a mimic and pGL3-CAPN6-MUT plasmids, cells in the group C were sequentially transfected with miR-216a mimic NC and pGL3-CAPN6-WT, and cells in the group D were sequentially transfected with miR-216a mimic NC and pGL3-CAPN6- MUT plasmids. At 36 h of cultivation, cells from each group were collected and the relative luciferase activity was calculated by the dual-luciferase reporter gene assay kit. Results Compared with the group V, group I had lower cell proliferation activity and percentage of scratch front migration distance, and fewer invasive cells at 48 h of cultivation (all P< 0.01). Compared with the group IV, group II had higher cell proliferation activity and percentage of scratch front migration distance, and more invasive cells (all P<0.01). Compared with the group I. group III had higher cell proliferation activity and percentage of scratch front migration distance, and more invasive cells (all P<0.01). Compared with the group II, group III had lower cell proliferation activity and percentage of scratch front migration distance, and fewer invasive cells (all P<0.01). Compared with group V, the relative expression level of miR-216a of cells in the group I was much higher (P<0.01). Compared with the group IV, the relative expression levels of CAPN6 protein and p-STAT3/STAT3 in the group II were much higher at 24 h of cultivation, while the relative expression levels of CAPN6 protein and p-STAT3/ STAT3 were lower in the group III. Compared with the group V, the relative expression levels of CAPN6 protein and p- STAT3/STAT3 in the group I were lower. Compared with group I, the relative expression levels of CAPN6 protein and p-STAT3/STAT3 in the group III were higher. Compared with the group B. group A had lower cell luciferase activity (P< 0.05). Conclusions Over-expression of miR-216a may inhibit the proliferation, invasion, and migration of Hela cells. There is a targeted relationship between miR-216a and CAPN6 gene in HeLa cells. MiR-216a may inhibit the proliferation, migration, and invasion of HeLa by regulating the expression of CAPN6 gene. [ABSTRACT FROM AUTHOR]

Objective To observe change of proliferation, migration and invasion abilities of pancreatic cancer cells with over-/down-expression of circSTON2, and to preliminarily investigate the biological function of circSTON2 in pancreatic cancer. Methods Human pancreatic cancer cell line PANC-1 was in vitro cultured. CircSTON2 over-expression group, circSTON2 down-expression group, and control group were established. Plasmid transfection and siRNA interference were used to transfect the circSTON2 overexpression plasmid and circSTON2-siRNA interference plasmid and blank control plasmid into the above groups. At 24, 36 and 48 hours of culture, CCK-8 assay was used to detect cell proliferation and Transwell assay was used to detect cell migration and invasion. Results At 24, 36 and 48 hours of culture, cell proliferation ability was as follows: circSTON2 over-expression group > control group > circSTON2 down-expression group (all P<0. 05); the number of migration cells and the number of invasion cells were as follows: circSTON2 over-expression group > control group > circSTON2 down-expression group (all P<0. 05）. Conclusions The over-expression of circSTON2 promotes proliferation, migration, and invasion of pancreatic cancer cells. However, the effect of down-expression of circSTON2 is the opposite. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of Fusobacterium nucleatum and microRNA-497(miR-497) on the proliferation, invasion and migration of colorectal cancer cells, and to analyze their regulatory relationships. Methods Colorectal cancer cell line HCT116 was transfected with miR-497 overexpression plasmid miR-497 mimic and was randomly divided into the infection index (MOI) 100 group, MOI 200 group, MOI 500 group, and MOI 1 000 group. They were co-cultured with Fusobacterium nucleatum with MOI of 100, 200, 500 and 1 000, respectively. Real-time fluorescent quantitative PCR was used to detect miR-497 in each group. The treatment concentration of the bacteria with the lowest expression of miR-497 was selected as the subsequent action concentration of Fusobacterium nucleatum. HCT116 cells were randomly divided into the control group, miR-497 over-expression group, miR-497 down-expression group, miR-497 over-expression negative control group and miR-497 down-expression negative control group, respectively. Cells in the control group were cultured without treatment. Cells in the miR-497 over-expression group, miR-497 down-expression group, over-expression negative control group, and down-expression negative control group were transfected with miR-497 mimics, miR497 inhibitor, mimic NC, and inhibitor NC, respectively, by Lipofectamine 2000. Cell proliferation ability was observed by CCK-8 assay, cell invasion ability was observed by Transwell assay, and cell migration ability was observed by Scratch healing assay. HCT116 cells were randomly divided into the control group, miR-497 over-expression group, overexpression negative control group, and over-expression + Fusobacterium nucleatum group, respectively. Cells in the control group were cultured without treatment, and cells in the miR-497 over-expression group were transfected with miR-497 mimic, while cells in the over-expression negative control group were transfected with mimic NC. After transfecting miR-497 mimic, cells in the overexpression + Fusobacterium nucleatum group were co-cultured with selected concentration of Fuso⁃ bacterium nucleatum. The cell proliferation ability was observed by CCK-8 assay, the cell invasion ability was observed by Transwell assay, and the cell migration ability was observed by Scratch healing assay. Results The miR-497 expression was as follows: MOI 100 group >MOI 200 group >MOI 500 group >MOI 1 000 group (all P<0. 05), and MOI 1 000 was selected as the subsequent action concentration of Fusobacterium nucleatum. Cell proliferation rate, the number of invasive cells and migration rate were as follows： miR-497 down-expression group > control group, overexpression negative control group, down-expression negative control group > miR-497 over-expression group (all P<0. 05). Cell proliferation rate, the number of invasive cells, and migration rate were as follows: miR-497 overexpression group < overexpression + Fusobacterium nucleatum group < control group, overexpression negative control group (all P<0. 05). Conclusion Fusobacterium nucleatum can promote the proliferation, invasion and migration of colorectal cancer cells through negative regulation of miR-497. [ABSTRACT FROM AUTHOR]

The role of cathepsin K (CTSK) expression in the pathogenesis and progression of gastric cancer (GC) remains unclear. Hence, the primary objective of this study is to elucidate the precise expression and biological role of CTSK in GC by employing a combination of bioinformatics analysis and in vitro experiments. Our findings indicated a significant upregulation of CTSK in GC. The bioinformatics analysis revealed that GC patients with a high level of CTSK expression exhibited enrichment of hallmark gene sets associated with angiogenesis, epithelial–mesenchymal transition (EMT), inflammatory response, KRAS signaling up, TNFα signaling via KFκB, IL2-STAT5 signaling, and IL6-JAK-STAT3 signaling. Additionally, these patients demonstrated elevated levels of M2-macrophage infiltration, which was also correlated with a poorer prognosis. The results of in vitro experiments provided confirmation that the over-expression of CTSK leads to an increase in the proliferative and invasive abilities of GC cells. However, further evaluation was necessary to determine the impact of CTSK on the migration capability of these cells. Our findings suggested that CTSK has the potential to facilitate the initiation and progression of GC by augmenting the invasive capacity of GC cells, engaging in tumor-associated EMT, and fostering the establishment of an immunosuppressive tumor microenvironment (TME). [ABSTRACT FROM AUTHOR]

• Integrins facilitate epithelial cell adhesion to the extracellular matrix, including the basement membrane. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. • Integrins are composed of 18 α and 8 β subunits in mammals, which come together as 24 heterodimers that bind distinct extracellular matrix proteins. • Integrins play a critical role in the biology of cancers, including carcinomas that develop from transformed epithelial cells. In some instances, they promote cancer development, growth and metastasis. In other instances, they inhibit the cancer phenotype. In most instances, the factors that determine whether an integrin can promote or inhibit the cancer phenotype remain undefined and thus hinders efforts to target integrins for the treatment of human cancers. • Integrins can signal in cancer cells via extracellular matrix-dependent and -independent mechanisms. Thus, abrogating integrin:extracellular matrix ligation may be insufficient for the treatment of cancer. Novel strategies to target integrin signaling in cancer are needed. Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues required for tissue morphogenesis, differentiation, function, and homeostasis. Epithelial cell adhesion to the extracellular matrix (i.e., basement membrane) plays a critical role in organizing epithelial tissues, separating the epithelial cells from the stroma. Epithelial cell detachment from the basement membrane classically results in death, though detachment or invasion through the basement membrane represents a critical step in carcinogenesis. Epithelial cells bind to the extracellular matrix via specialized matrix receptors, including integrins. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. The role of integrins in the development, growth, and dissemination of multiple types of carcinomas has been investigated by numerous methodologies, which has led to great complexity. To organize this vast array of information, we have utilized the "Hallmarks of Cancer" from Hanahan and Weinberg as a convenient framework to discuss the role of integrins in the pathogenesis of cancers. This review explores this biology and how its complexity has impacted the development of integrin-targeted anti-cancer therapeutics. [ABSTRACT FROM AUTHOR]

The present study was aimed to explore the effect of triazole on growth and viability of liver cancer cells. Cell growth was examined using the MTT test and expression of several proteins was assessed by western blotting assay. The Matrigel-coated Transwell assay was employed to examine the infiltration of cells. The data from MTT assay showed that MHCC97H and H4TG liver cancer cell viability was inhibited by triazole in a concentration-dependent manner. After treatment with 0.5, 1.0, 2.0, 4, 8, and 16 µM doses of triazole, the rate of H4TG cell viability was decreased to 96, 73, 58, 39, 29, and 28%, respectively. Treatment of MHCC97H cells with 0.5, 1.0, 2.0, 4, 8, and 16 µM doses of triazole resulted in a reduction in cell viability to 94, 70, 53, 35, 22, and 21%, respectively. Triazole treatment also led to a significant reduction in MHCC97H cell invasiveness compared to the control cells. In MHCC97H cells treated with triazole, there was a noticeable decrease in the levels of p-ERK1/2, and p-Akt protein expression. Treatment of MHCC97H cells with triazole resulted in a prominent increase in p-p38 level. In summary, triazole inhibits growth and viability of liver cancer cells through targeting the activation of p-ERK1/2 and Akt proteins. Therefore, triazole may be investigated further as a therapeutic agent for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Background: Butyrate is a common short-chain fatty acids (SCFA), and it has been demonstrated to regulate the development of breast cancer (BC), while the underlying mechanism is still unreported. Methods: Gas chromatography was used to measure the amounts of SCFA (acetate, propionate, and butyrate) in the feces. Cell viability was measured by the CCK-8 assay. The wound healing assay demonstrated cell migration, and the transwell assay demonstrated cell invasion. The levels of protein and gene were determined by western blot assay and RT-qPCR assay, respectively. Results: The levels of SCFA were lower in the faecal samples from BC patients compared to control samples. In cellular experiments, butyrate significantly suppressed the cell viability, migration and invasion of T47D in a dose-dependent manner. In animal experiments, butyrate effectively impeded the growth of BC tumors. Toll like receptor 4 (TLR4) was highly expressed in the tumors from BC patients. Butyrate inhibited the expression of TLR4. In addition, butyrate promoted the expression of cuproptosis-related genes including PDXK (pyridoxal kinase) and SLC25A28 (solute carrier family 25 member 28), which was lowly expressed in BC tumors. Importantly, overexpression of TLR4 can reverses the promotion of butyrate to PDXK and SLC25A28 expression and the prevention of butyrate to the malignant biological behaviors of T47D cells. Conclusion: In summary, butyrate inhibits the development of BC by facilitating the expression of PDXK and SLC25A28 through inhibition of TLR4. Our investigation first identified a connection among butyrate, TLR4 and cuproptosis-related genes in BC progression. These findings may provide novel target for the treatment of BC. [ABSTRACT FROM AUTHOR]

Sakuranin is a flavanone which is a class of flavonoids found abundantly in Prunus species. Flavonoids have been long known for their anticancer properties against a range of human cancers. However, there are no previous reports on the anticancer effects of sakuranin flavanone molecule. This study was designed to study the anticancer effects of sakuranin against human oropharyngeal carcinoma cells along with investigating its effects on caspase-mediated apoptosis, mitochondrial membrane potential (MMP) loss, cell migration and invasion and m-TOR/PI3K/AKT signalling pathway. MTT assay was used to study effects on cell viability. The apoptotic studies were carried out through AO/EB staining, annexin V/FITC staining, comet assay and western blotting assay. Transwell chambers assay was used to study effects on cell migration and invasion. Flow cytometry was used to study effects of Sakuranin on mitochondrial membrane potential loss (MMP). Finally, western blotting was used to investigate m-TOR/PI3K/AKT signalling pathway. Results indicated that Sakuranin led to potent cell proliferation inhibition in a dosedependent manner. Sakuranin also induced apoptotic cell death as indicated by fluorescence microscopy and annexin V/FITC staining assays. The apoptotic induction was mediated via activation of caspase-3, caspase-9, and Bax while as it led to downregulation of Bcl-2. Sakuranin also caused inhibition of cell migration and cell invasion along with causing significant decrease in MMP. Sakuranin also caused inhibition of expressions of proteins related with m-TOR/PI3K/AKT signalling pathway. In conclusion, the current findings clearly indicate anticancer effects of Sakuranin flavanone in human oropharyngeal cancer cells and are mediated via caspase activated apoptosis, inhibition of cell migration and invasion, loss of mitochondrial membrane potential and targeting m-TOR/PI3K/AKT signalling pathway. [ABSTRACT FROM AUTHOR]