Search

Purpose: Lung cancer is one of the leading causes of death worldwide. Recent studies have shown that circular RNAs are dysregulated in a variety of cancers, but the mechanism in lung cancer is still indistinct. In our work, we explored the action mechanism of circLDLRAD3 in lung cancer. Methods: The abundance of circLDLRAD3, microRNA-497-5p (miR-497-5p) and platelet-type PFK (PFKP) was measured by real-time quantitative polymerase chain reaction (RT-qPCR) in lung cancer. Meanwhile, the level of PFKP was quantified by western blot. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, transwell assay, wound healing assay, flow cytometry, western blot, immunohistochemical (IHC) assay and glycolysis metabolism analysis were performed for functional analyses. Furthermore, the interplay between miR-497-5p and circLDLRAD3 or FKPF was detected by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Eventually, the in vivo experiments were applied to measure the role of circLDLRAD3. Result: The levels of circLDLRAD3 and PFKP were increased. Silencing circLDLRAD3 inhibited cell viability, proliferation, migration, invasion and glycolysis metabolism and promoted cell apoptosis in lung cancer cells. In mechanism, circLDLRAD3 regulated PFKP level as a miR-497-5p sponge. MiR-497-5p suppressed the progression of lung cancer by inhibiting PFKP. In addition, circLDLRAD3 knockdown also inhibited tumor growth in vivo. Conclusion: CircLDLRAD3 promoted the development of lung cancer through increasing PFKP expression by regulating miR-497-5p, which also provided a potential targeted therapy for lung cancer treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear. Methods We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS’s function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC. Results We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes. Conclusion The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS’s role in regulating angiogenesis and provides a novel target for EC treatment.

Objective: To study the relationship between serum long chain non coding RNA-human plasmacytoma transformation and migration gene 1 (LncRNA-PVT1), microribonucleic acid-497-5p (miR-497-5p) expression and lung function and prognosis in patients with chronic obstructive pulmonary disease (COPD) with lung cancer. Methods: 116 patients with COPD combined with lung cancer underwent concurrent surgical treatment admitted to Linyi Cancer Hospital from March 2018 to March 2020 were selected as the observation group, while 50 patients with simple COPD during the same period were included in the control group. The relative expression levels of serum LncRNA-PVT1 and miR-497-5p and lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, percentage of forced expiratory volume in the first second to predicted value (FEV1%pred)] were compared between two groups. The correlation between serum LncRNA-PVT1, miR-497-5p expression and lung function indexes in patients with COPD with lung cancer were analyzed by Pearson test. Patients with COPD with lung cancer were followed up for 3 years after operation, the prognostic factors of patients with COPD with lung cancer were analyzed by multivariate Cox regression model. 3 years overall survival rate of patients with low expression and high expression of LncRNA-PVT1 and miR-497-5p were analyzed by drawn Kaplan-Meier survival curve. Results: Compared with control group, the expression level of serum LncRNA-PVT1 in observation group was significantly increased (P<0.05), and the expression level of miR-497-5p was significantly decreased (P<0.05). Compared with control group, FEV1, FEV1% pred and FEV1/FVC in observation group were significantly lower(P<0.05). Pearson test results showed that, serum LncRNA-PVT1 was negatively correlated with FEV1, FEV1% pred and FEV1/FVC in patients with COPD with lung cancer (P<0.05); serum miR-497-5p was positively correlated with FEV1, FEV1% pred and FEV1/FVC(P<0.05). The Kplan-Meier survival curve showed that, the 3 years overall survival rate in LncRNA-PVT1 high expression group was 29.23%, which was significantly lower than 47.73% in LncRNA-PVT1 low expression group (P<0.05). 3 years overall survival rate in miR-497-5p high expression group was 46.77%, which was significantly higher than 23.40% in miR-497-5p low expression group (P<0.05). Multivariate Cox regression analysis showed that, lymph node metastasis, TNM stage IIIa, poor differentiation of tumor tissue, high expression of LncRNA-PVT1 and low expression of miR-497-5p were risk factors for prognosis of patients with COPD with lung cancer (P<0.05). Conclusion: LncRNA-PVT1 is highly expresse and miR-497-5p is lowly expresse in the serum of patients with COPD with lung cancer, the expression level is relate to lung function indexes, and the higher the expression level of LncRNA-PVT1 and the lower the expression level of miR-497-5p, the lower the 3 years overall survival rate. [ABSTRACT FROM AUTHOR]

Background: Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear. Methods: We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS's function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC. Results: We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes. Conclusion: The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS's role in regulating angiogenesis and provides a novel target for EC treatment. [ABSTRACT FROM AUTHOR]

Objective To explore the effects of lncRNA ANCR regulating miR-497-5p on vascular lumen formation, apoptosis and PI3K/AKT signaling pathway of gastric cancer cells. Methods Gastric cancer cells were collected and divided into gastric cancer cell (GC) group, gastric cancer cell +lncRNA ANCR-NC (AN) group, gastric cancer cell + lncRNA ANCR overexpressed plasmid (AM) group, gastric cancer cell + lncRNA ANCR siRNA (AI) group, gastric cancer cells + miR-497-5p-NC (MN) group, gastric cancer cells + miR-497-5p siRNA (MI) group, gastric cancer cells +miR-497-5p mimics (MM) group, and gastric cancer cells + lncRNA ANCR siRNA+miR-497-5p mimics (IM) group. Vascular lumen formation was observed by lumen formation assay, cell apoptosis was detected by PI staining method, and protein expression of PI3K and AKT was detected by western blotting. The interaction between lncRNA ANCR and miR-497-5p was confirmed by double luciferase reporting assay. Results Compared with AN group and MN group, the apoptosis rate of AM group and MI group was significantly decreased (P＜0.05), the number of vascular lumen formation and the expression of PI3K and AKT protein were significantly increased (P＜0.05). Compared with AM and MI groups, the apoptosis rate of AI and MM groups was significantly increased (P＜0.05), while the number of vascular lumen formation and the expression of PI3K and AKT protein were significantly decreased (P＜0.05). Compared with AI and MM groups, the apoptosis rate of IM group was significantly increased (P＜0.05), the number of vascular lumen formation and the expression of PI3K and AKT protein were significantly decreased (P＜0.05). The results of double luciferase report showed that transfection of lncRNA ANCR could significantly reduce the luciferase activity of miR-497-5p-3′-UTR-WT (P＜0.05), but had no significant effect on mutant genes (P＞0.05). Conclusion Inhibition of lncRNA ANCR can effectively inhibit the formation of vascular lumen, promote cell apoptosis, and inhibit the expression of PI3K/AKT signaling pathway in gastric cancer cells, which may be related to the targeted activation of miR-497-5p.

Wei W, Mo X, Yan L, et al. Cancer Manag Res. 2020;12:15–30. We, the Editor and Publisher of the journal Cancer Management and Research have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Epithelial-mesenchymal transition (EMT) is a vital pathological feature of silica-induced pulmonary fibrosis. However, whether circRNA is involved in the process remains unclear. The present study aimed to investigate the role of circPVT1 in the silica-induced EMT and the underlying mechanisms. We found that an elevated expression of circPVT1 promoted EMT and enhanced the migratory capacity of silica-treated epithelial cells. The isolation of cytoplasmic and nuclear separation assay showed that circPVT1 was predominantly expressed in the cytoplasm. RNA immunoprecipitation assay and RNA pull-down experiment indicated that cytoplasmic-localized circPVT1 was capable of binding to miR-497-5p. Furthermore, we found that miR-497-5p attenuated the silica-induced EMT process by targeting transcription factor 3 (TCF3), an E-cadherin transcriptional repressor, in the silica-treated epithelial cells. Collectively, these results reveal a novel role of the circPVT1/miR-497-5p/TCF3 axis in the silica-induced EMT process in lung epithelial cells. Once validated, this finding may provide a potential theoretical basis for the development of interventions and treatments for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the molecular mechanism by which miR-497-5p regulates neuronal injury after ischemic stroke through the BDNF/TrkB/Akt signaling pathway. PC12 cells were used to construct a stroke injury model by oxygen-glucose deprivation/reoxygenation (OGD/R). The expression level of miR-497-5p was measured by RT-qPCR. CCK-8 kit was used to detect cell viability. Cell apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. MDA and SOD detection kits were used to detect MDA content and SOD activity. A double luciferase reporter system was used to verify the targeting relationship between miR-497-5p and BDNF. The expression of BDNF, TrkB, p-TrkB, Akt and p-Akt was detected by Western blot. We have found that miR-497-5p expression was inhibited after treatment with OGD/R. Simultaneously, cell apoptosis, MDA content and ROS were upregulated, while cell viability and SOD were significantly decreased in PC12 cells. The effects of OGD/R on PC12 cells were reversed with the downregulation of miR-497-5p. A double luciferase reporter assay demonstrated that miR-497-5p negatively targets BDNF. BDNF inhibited cell apoptosis and oxidative stress injury in PC12 cells. These findings suggest that miR-497-5p aggravates neuronal injury in experimental model of ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Background. Cervical cancer is prevalent throughout the world, and microRNA-497-5p (miR-497-5p) plays an important role in its development. However, the specific mechanism by which miR-497-5p targets the transferrin receptor (TFRC) during cervical cancer development has not been clarified. Objectives. The aim of the study was to unravel TFRC expression and its role in cervical cancer cells, as well as the impact of the miR-497-5p/TFRC axis on cervical cancer cells. Materials and methods. The target mRNA was determined through differential analysis, followed by the evaluation of its impact on survival and clinical staging. Then, quantitative real-time polymerase chain reaction (qPCR) was conducted to analyze the TFRC mRNA level in cervical cancer cells and normal cervical epithelial cells. Western blot (WB) was utilized to examine the expression levels of TFRC, cleaved caspase-3, cleaved caspase-9, and epithelial-mesenchymal transition (EMT)-related proteins. The miRNAs upstream of the target mRNA were predicted, and Pearson correlation analysis was performed, followed by the validation through the dual-luciferase reporter assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were performed to analyze cancer cell viability, followed by a transwell assay aimed at measuring cell migratory and invasive abilities. Finally, flow cytometry was conducted to examine cell apoptosis and cell cycle. Results. The transferrin receptor was significantly increased in cervical cancer cells and positively associated with clinical T and N stages. Silencing TFRC could constrain cell proliferative, migratory and invasive abilities, arrest the cell cycle and facilitate cell apoptosis in cervical cancer cells. The bioinformatics analysis showed a significantly negative correlation between miR-497-5p and TFRC in cervical cancer. Moreover, upregulated miR-497-5p hampered cervical cancer progression and decreased TFRC expression. The overexpression of TFRC reversed the suppressive impact of miR-497-5p overexpression on cervical cancer progression. Conclusions. The modulatory role of the miR-497-5p/TFRC axis was confirmed in cervical cancer cells. This axis may present a new avenue for the diagnosis of cervical cancer and provide a novel target for cervical cancer treatment. [ABSTRACT FROM AUTHOR]

Circular RNA dipeptidyl peptidase 4 (circDPP4) has been confirmed as a novel oncogene in prostate cancer (PCa). In this study, we aimed to explore the underlying mechanism of circDPP4 in PCa progression. Levels of circDPP4, microRNA (miR)-497-5p, glutamate dehydrogenase 1 (GLUD1), proliferating cell nuclear antigen (PCNA), BCL2 associated X, apoptosis regulator (Bax), E-cadherin and Ki67 were gauged by a quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, or immunohistochemical method. We assessed the roles of variables in PCa cell phenotypes by measuring cell growth, apoptosis, motility and invasiveness. We performed RNA immunoprecipitation (RIP) and dual-luciferase reporter assays to confirm the interactions of circDPP4/miR-497-5p and miR-497-5p/GLUD1. A xenograft model was established to gauge the effect of circDPP4 in the tumorigenicity of PCa cells. PCa tumor tissues and cell lines revealed higher levels of circDPP4 and GLUD1 and a lower expression of miR-497-5p than controls. CircDPP4 silencing hindered the growth, motility and invasiveness of PCa cells. Conversely, silencing circDPP4 enhanced PCa cell apoptosis. Mechanistic analysis showed that circDPP4 functioned as a miR-497-5p sponge to reduce the suppressive action of miR-497-5p on GLUD1, which was validated as a direct miR-497-5p target. Furthermore, circDPP4 knockdown weakened the tumorigenicity of PCa cells. CircDPP4 facilitated PCa process by mediating the miR-497-5p/GLUD1 axis, providing a possible therapy target for PCa. [ABSTRACT FROM AUTHOR]

Abstract Background Lung cancer is the most common and deadliest cancer worldwide, and approximately 90% of all lung cancer deaths are caused by tumor metastasis. Tumor-derived exosomes could potentially promote tumor metastasis through the delivery of metastasis-related molecules. However, the function and underlying mechanism of exosomal long noncoding RNA (lncRNA) in lung cancer metastasis remain largely unclear. Methods Cell exosomes were purified from conditioned media by differential ultracentrifugation and observed using transmission electron microscopy, and the size distributions were determined by nanoparticle tracking analysis. Exosomal lncRNA sequencing (lncRNA-seq) was used to identify long noncoding RNAs. Cell migration and invasion were determined by wound-healing assays, two-chamber transwell invasion assays and cell mobility tracking. Mice orthotopically and subcutaneously xenografted with human cancer cells were used to evaluate tumor metastasis in vivo. Western blot, qRT‒PCR, RNA-seq, and dual-luciferase reporter assays were performed to investigate the potential mechanism. The level of exosomal lncRNA in plasma was examined by qRT‒PCR. MS2-tagged RNA affinity purification (MS2-TRAP) assays were performed to verify lncRNA-bound miRNAs. Results Exosomes derived from highly metastatic lung cancer cells promoted the migration and invasion of lung cancer cells with low metastatic potential. Using lncRNA-seq, we found that a novel lncRNA, lnc-MLETA1, was upregulated in highly metastatic cells and their secreted exosomes. Overexpression of lnc-MLETA1 augmented cell migration and invasion of lung cancer. Conversely, knockdown of lnc-MLETA1 attenuated the motility and metastasis of lung cancer cells. Interestingly, exosome-transmitted lnc-MLETA1 promoted cell motility and metastasis of lung cancer. Reciprocally, targeting lnc-MLETA1 with an LNA suppressed exosome-induced lung cancer cell motility. Mechanistically, lnc-MLETA1 regulated the expression of EGFR and IGF1R by sponging miR-186-5p and miR-497-5p to facilitate cell motility. The clinical datasets revealed that lnc-MLETA1 is upregulated in tumor tissues and predicts survival in lung cancer patients. Importantly, the levels of exosomal lnc-MLETA1 in plasma were positively correlated with metastasis in lung cancer patients. Conclusions This study identifies lnc-MLETA1 as a critical exosomal lncRNA that mediates crosstalk in lung cancer cells to promote cancer metastasis and may serve as a prognostic biomarker and potential therapeutic target for lung cancer diagnosis and treatment.

Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell dysfunction remains to be elucidated. Methods: An in vitro AS cell model was established by exposing human umbilical vein endothelial cells (HUVECs) to 100 μg/mL ox-LDL for 24 h. The assessment of endothelial cell function included evaluating cell viability, caspase-3 activity, inflammatory factors, and oxidative markers. Molecular mechanisms were elucidated through quantitative real-time PCR, Western blot analysis, and luciferase reporter assays. Results: Our investigation revealed that exposure to ox-LDL led to an upregulation in miR-497-5p and p-p38 levels, while downregulating the expression of vascular endothelial growth factor A (VEGFA) and phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) in HUVECs. Ox-LDL exposure resulted in decreased cell viability and angiogenic capacity, coupled with increased apoptosis, inflammation, and oxidative stress in HUVECs, partially mediated by the upregulation of miR-497-5p. We confirmed VEGFA as a direct target of miR-497-5p. Interfering with VEGFA expression significantly reversed the effects mediated by miR-497-5p silencing in HUVECs exposed to ox-LDL. Conclusions: In summary, our findings demonstrate that miR-497-5p exacerbates ox-LDL-induced dysfunction in HUVECs through the activation of the p38/MAPK pathway, mediated by the targeting of VEGFA.

The pivotal role of lncRNAs in osteoporosis progression and development necessitates a comprehensive exploration of the functional and precise molecular mechanisms underlying lncRNA SNHG1's regulation of osteoblast differentiation and calcification. The study involved inducing BMSCs cells to differentiate into osteoblasts, followed by transfections of miR-497-5p inhibitors, pcDNA3.1-SNHG1, sh-HIF1AN, miR-497-5p mimics, and respective negative controls into BMSCs. Quantitative PCR (qPCR) was employed to assess the expression of SNHG1 and miR-497-5p. Western Blotting was conducted to measure the levels of short stature-related transcription factor 2 (RUNX2), osteopontin (OPN), osteocalcin (OCN), and HIF1AN. Alkaline phosphatase (ALP) activity was determined using appropriate assay kits. Calcium nodule staining was performed through Alizarin red staining. Dual luciferase reporter gene assays were executed to validate the interaction between SNHG1 and miR-497-5p, as well as HIF1AN. Throughout osteogenic differentiation, there was a down-regulation of SNHG1 and HIF1AN, in contrast to an elevation in miR-497-5p levels. Direct interactions between miR-497-5p and both SNHG1 and HIF1AN were observed. Notably, SNHG1 exhibited the ability to modulate HIF1AN by influencing miR-497-5p, thereby inhibiting osteogenic differentiation. Functioning as a competitive endogenous RNA, lncRNA SNHG1 exerts an inhibitory influence on osteogenic differentiation via the miR-497-5p/HIF1AN axis. This highlights the potential for lncRNA SNHG1 to emerge as a promising therapeutic target for osteoporosis. The study's findings pave the way for a novel target strategy in the future treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM), a prevalent complication during the gestation period, has been linked to impaired proliferation and migration of trophoblasts causing placental maldevelopment. We previously found that lncRNA X‐inactive specific transcript (XIST) played an essential role in GDM progression. Here, we investigated the precise biological functions as well as the upstream and downstream regulatory mechanisms of XIST in GDM. We found that XIST and forkhead box O1 (FOXO1) were conspicuously upregulated and miR‐497‐5p and methyltransferase‐like 14 (METTL14) were downregulated in the placentas of GDM patients. XIST silencing facilitated proliferation and migration and inhibited cell apoptosis and cell cycle arrest in HG‐cultured HTR8/SVneo cells. METTL14 inhibited XIST expression through m6A methylation modification. XIST overexpression abrogated the positive effect of METTL14 overexpression on HG‐cultured HTR8/SVneo cell progression. MiR‐497‐5p and FOXO1 are downstream regulatory genes of XIST in HTR8/SVneo cells. Reverse experiments illustrated that XIST mediated HTR8/SVneo cell functions by regulating the miR‐497‐5p/FOXO1 axis. Additionally, XIST silencing augmented glucose tolerance and alleviated fetal detrimental changes in GDM rats. To conclude, METTL14‐mediated XIST silencing facilitated proliferation and migration and inhibited cell apoptosis and cell cycle arrest in HG‐cultured HTR8/SVneo cells via the miR‐497‐5p/FOXO1 axis, thereby alleviating GDM progression in rats. [ABSTRACT FROM AUTHOR]

Abstract Background Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. Methods In this research, deep sequencing of circRNAs from OC samples and paired adjacent normal tissues was performed to establish expression profiles and circ-PHC3 levels between the groups further compared using RT-qPCR. The effects of ectopic overexpression of miR-497-5p and SOX9 and siRNA-mediated knockdown of circ-PHC3 and an miR-497-5p inhibitor were explored to clarify the regulatory mechanisms underlying circ-PHC3 activity in OC proliferation and metastasis. Information from public databases and the luciferase reporter assay were further utilized to examine the potential correlations among circ-PHC3, miR-497-5p and SOX9. Results Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. Conclusion Taken together, our findings suggest that circ-PHC3 enhances OC progression through functioning as an miR-497-5p sponge to promote SOX9 expression, supporting its potential as a promising candidate target for OC therapy.

As the most common histological subtype of primary lung cancer, lung adenocarcinoma (LUAD) causes enormous cancer deaths worldwide. Radiotherapy has been frequently used in LUAD cases, and radiosensitivity is vital for LUAD therapy. This research sought to explore the genetic factors affecting radiosensitivity in LUAD and inner mechanisms. LINC00511, miR-497-5p, and SMAD3 expression in LUAD cells were detected via qRT-PCR and western blot. CCK-8 assays, colony formation, and flow cytometry assays were employed to explore the cell viability, apoptosis, and radiosensitivity in PC-9 and A549 cells. The targeting relationship between LINC00511, miR-497-5p, and SMAD3 was verified by dual luciferase reporter assay. Furthermore, xenograft experiments were performed for the in vivo verification. In conclusion, LINC00511 was overexpressed in LUAD cells, which downregulated downstream miR-497-5p expression and mediately led to SMAD3 activation. LINC00511 downregulation suppressed cell viability while enhanced apoptosis rate in LUAD cells. Also, LINC00511 and SMAD3 were overexpressed, while miR-497-5p was downregulated in LUAD cells exposed to 4Gy irradiation treatment. Moreover, LINC00511 inhibition could block SMAD3 expression and promoted the radiosensitivity both in vitro and in vivo. These findings uncover LINC00511 knockdown promoted miR-497-5p expression and subsequently led to lower SMAD3 level, which enhanced radiosensitivity in LUAD cells. LINC00511/miR-497-5p/SMAD3 axis could be of considerable potential to enhance radiosensitivity in LUAD.

Objective: This study evaluated the regulatory effect of Tetramethylpyrazine (TMP) on the spinal cord injury (SCI) rat model and clarified the neuroprotective mechanism of TMP on SCI. Methods: An SCI rat model was generated and treated with TMP injections for two weeks. miR-497-5p and EGFL7 expression changes were evaluated, motor function recovery after SCI was assessed by BBB score test and footprint analysis, lesions of rat spinal cord were assessed by HE staining and TUNEL staining; angiogenesis was assessed by immunoblotting for CD31; inflammatory factor levels were detected by ELISA. EGFL7 was verified as a target of miR-497-5p by bioinformatics website analysis and luciferase reporter gene assay. H2O2-injured neurons were cultured in vitro to explore the effect of TMP. Results: After SCI, miR-497-5p was upregulated while EGFL7 was downregulated in rats. TMP inhibited apoptosis and promoted angiogenesis, nerve regeneration, and repair of nerve defects by reducing miR-497-5p and increasing EGFL7 expression. miR-497-5p targeted EGFL7. In addition, TMP hindered neuronal inflammation and apoptosis induced by H2O2 in vitro. Conclusion: TMP promotes angiogenesis by downregulating miR-497-5p to target EGFL7, and promotes nerve regeneration and repair of nerve defects in rats with SCI.

Background: Lung cancer is the most common and deadliest cancer worldwide, and approximately 90% of all lung cancer deaths are caused by tumor metastasis. Tumor-derived exosomes could potentially promote tumor metastasis through the delivery of metastasis-related molecules. However, the function and underlying mechanism of exosomal long noncoding RNA (lncRNA) in lung cancer metastasis remain largely unclear. Methods: Cell exosomes were purified from conditioned media by differential ultracentrifugation and observed using transmission electron microscopy, and the size distributions were determined by nanoparticle tracking analysis. Exosomal lncRNA sequencing (lncRNA-seq) was used to identify long noncoding RNAs. Cell migration and invasion were determined by wound-healing assays, two-chamber transwell invasion assays and cell mobility tracking. Mice orthotopically and subcutaneously xenografted with human cancer cells were used to evaluate tumor metastasis in vivo. Western blot, qRT‒PCR, RNA-seq, and dual-luciferase reporter assays were performed to investigate the potential mechanism. The level of exosomal lncRNA in plasma was examined by qRT‒PCR. MS2-tagged RNA affinity purification (MS2-TRAP) assays were performed to verify lncRNA-bound miRNAs. Results: Exosomes derived from highly metastatic lung cancer cells promoted the migration and invasion of lung cancer cells with low metastatic potential. Using lncRNA-seq, we found that a novel lncRNA, lnc-MLETA1, was upregulated in highly metastatic cells and their secreted exosomes. Overexpression of lnc-MLETA1 augmented cell migration and invasion of lung cancer. Conversely, knockdown of lnc-MLETA1 attenuated the motility and metastasis of lung cancer cells. Interestingly, exosome-transmitted lnc-MLETA1 promoted cell motility and metastasis of lung cancer. Reciprocally, targeting lnc-MLETA1 with an LNA suppressed exosome-induced lung cancer cell motility. Mechanistically, lnc-MLETA1 regulated the expression of EGFR and IGF1R by sponging miR-186-5p and miR-497-5p to facilitate cell motility. The clinical datasets revealed that lnc-MLETA1 is upregulated in tumor tissues and predicts survival in lung cancer patients. Importantly, the levels of exosomal lnc-MLETA1 in plasma were positively correlated with metastasis in lung cancer patients. Conclusions: This study identifies lnc-MLETA1 as a critical exosomal lncRNA that mediates crosstalk in lung cancer cells to promote cancer metastasis and may serve as a prognostic biomarker and potential therapeutic target for lung cancer diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Circular RNAs exert vital functions in the pathogenesis of osteosarcoma (OS). Circ_001422 has been confirmed to be involved in regulating OS progression, but its specific mechanism has not been clearly studied. This work aimed to analyze circ_001422's role in OS cell biological behaviors and the possible molecular mechanisms. This work carried out reverse transcription‐quantitative polymerase chain reaction for detecting circ_001422, E2F3 and miR‐497‐5p levels, whereas Cell counting kit‐8 together with Transwell assays for measuring cell growth, migration as well as invasion abilities. Relation of miR‐497‐5p with E2F3, as well as circ_001422 with miR‐497‐5p was analyzed through dual‐luciferase reporter gene assay. Protein level was identified by western blot. According to our results, circ_001422 expression within OS tissue significantly increased compared with corresponding healthy samples. Inhibition of circ_001422 significantly decreased OS cell growth, invasion and migration. From mechanism research, miR‐497‐5p was proved as circ_001422's target, and E2F3 was miR‐497‐5p's target. Besides, miR‐497‐5p downregulation or E2F3 overexpression abolished circ_001422 inhibition‐mediated inhibition on OS cell proliferation, invasion and migration. Collectively, this study has first suggested circ_001422's role in enhancing OS proliferation, migration as well as invasion via miR‐497‐5p/E2F3 axis. Our results will offer new ideas and new anti‐OS targets. [ABSTRACT FROM AUTHOR]

Background: Accumulating studies have reported indispensable functions of circular RNAs (circRNA) in tumor progression through regulation of gene expression. However, circRNA expression profiles and functions in human ovarian carcinoma (OC) are yet to be fully established. Methods: In this research, deep sequencing of circRNAs from OC samples and paired adjacent normal tissues was performed to establish expression profiles and circ-PHC3 levels between the groups further compared using RT-qPCR. The effects of ectopic overexpression of miR-497-5p and SOX9 and siRNA-mediated knockdown of circ-PHC3 and an miR-497-5p inhibitor were explored to clarify the regulatory mechanisms underlying circ-PHC3 activity in OC proliferation and metastasis. Information from public databases and the luciferase reporter assay were further utilized to examine the potential correlations among circ-PHC3, miR-497-5p and SOX9. Results: Our results showed significant upregulation of circ-PHC3 in both OC cell lines and tissues. In the luciferase reporter assay, downregulation of circ-PHC3 led to suppression of metastasis and proliferation, potentially through targeted effects on the miR-497-5p/SOX9 axis in OC. SOX9 overexpression or miR-497-5p suppression rescued OC cell proliferation and invasion following silencing of circ-PHC3. Moreover, SOX9 inhibition induced restoration of OC cell invasion and proliferation under conditions of overexpression of miR-497-5p. Thus, circ-PHC3 appears to exert effects on cancer stem cell differentiation through regulation of the miR-497-5p/SOX9 axis. Conclusion: Taken together, our findings suggest that circ-PHC3 enhances OC progression through functioning as an miR-497-5p sponge to promote SOX9 expression, supporting its potential as a promising candidate target for OC therapy. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is an aggressive malignancy with poor prognosis. Accumulating studies have showed that long non‐coding RNA (lncRNA) is a crucial regulator in various tumorigenesis and progression including PC. This research aims to explore the roles and molecular mechanism of lncRNA cancer susceptibility candidate 9 (CASC9) in PC. Methods: The expression levels of lncRNA CASC9 and miR‐497‐5p were evaluated in PC tissues and paired adjacent healthy tissues by quantitative real‐time PCR. PC cell lines were transfected with lentivirus targeting lncRNA CASC9, and cells proliferation, migration and invasion tests were conducted. Dual luciferase reporter assays were also carried out to explore the relationship between lncRNA CASC9, miR‐497‐5p and Cyclin D1 (CCND1). Results: LncRNA CASC9 was significantly up‐regulated in PC tissues, while miR‐497‐5p expression was down‐regulated. Down‐regulation of lncRNA CASC9 in PC cells can significantly suppress the cell aggressiveness both in vitro and in vivo; moreover, knock‐down of miR‐497‐5p could neutralize this impact. Additionally, the luciferase activity assay has assured that CCND1 was a downstream target of miR‐497‐5p. Conclusion: LncRNA CASC9 can promote the PC progression by modulating miR‐497‐5p/CCND1 axis, which is potential target for PC treatment. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is characterized by elevated blood glucose during pregnancy, which may affect both the fetus and the pregnant woman. This study introduced the expression and regulatory ability of long non-coding RNA (lncRNA) DLX6 Antisense RNA 1 (DLX6-AS1) in patients with GDM, aiming to reveal the action potential and diagnostic value of DLX6-AS1. Methods: This study included 70 pregnant patients with GDM and 50 healthy pregnant women. DLX6-AS1 levels were determined using real-time quantitative polymerase chain reaction (RT-qPCR), and the diagnostic value of DLX6-AS1 was evaluated by receiver operating characteristic (ROC) curve. The GDM cell model was constructed using human chorionic trophoblast cells, and the cell proliferation capacity was assessed using cell counting kit-8 (CCK-8) method. Cell apoptosis was analyzed by flow cytometry. Moreover, luciferase assay was performed to evaluate the relationship between DLX6-AS1 and miR-497-5p. Results: DLX6-AS1 and blood glucose levels were markedly increased in GDM patients, and a positive correlation was observed between both levels (r = 0.7072, p < 0.0001). GDM affected the cell activity, while DLX6-AS1 silencing enhanced the proliferation activity, and suppressed cell apoptosis in GDM cell model via directly targeting miR-497-5p. miR-497-5p expression was low in GDM, and its content was affected by DLX6-AS1 silencing (p < 0.001). Furthermore, DLX6-AS1 exhibited a promising diagnostic function in GDM (area under the curve (AUC) = 0.937, sensitivity = 92.9%, specificity = 86.0%). Conclusions: DLX6-AS1 was positively expressed and mediated GDM through sponge miR-497-5p, suggesting it may be used as a diagnostic factor to predict the occurrence of GDM.

Liu WW, Li WD, Zhang YJ, Zhang ML. Cancer Manag Res. 2021;13:439–447. Following publication of the article, the authors raised concerns over the duplication of the two bar charts in Figure 5D. In addition, concerns were also raised about the duplication of images from Figure 2 with images from an unrelated article. Specifically, The image for Figure 2C, MDA-MB-231, miR-497-5p-inhibitor, has been duplicated with the image for Figure 2d, A549, inhibit-NC, from Ge H, Wang L, Chen W, Wang L. Mechanism of miR-760 Reversing Lung Cancer Immune Escape by Downregulating IDO1 and Eliminating Regulatory T Cells Based on Mathematical Biology. Computational and Mathematical Methods in Medicine. 2022;2022: Article ID 2960773. https://doi.org/10.1155/2022/2960773. When approached for an explanation, the authors were cooperative but were unable to provide a sufficient explanation for the image duplication or provide sufficient original data for their study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Circular RNAs (circRNAs) can function as functional molecules in hepatocellular carcinoma (HCC). Herein, circRNA superoxide dismutase 2 (circSOD2) was researched in HCC progression and immune system. The real-time polymerase chain reaction (qRT-PCR) was used for quantification of circSOD2, microRNA-497-5p (miR-497-5p) and Annexin A11 (ANXA11). Cell assays were performed by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and colony formation assays for proliferation, flow cytometry for apoptosis and cell cycle, wound healing assay for migration and transwell assay for migration/invasion. ANXA11 and metastatic protein levels were measured by western blot. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to analyze target binding. CD8+ T cell immunity was assessed by Immunohistochemistry (IHC) assay, and the effect of circSOD2 on programmed cell death 1 (PD-1) immune checkpoint inhibitors (anti-PD-1) therapy was evaluated by mice xenograft assay. CircSOD2 was upregulated in HCC tissues and cells. Knockdown of circSOD2 resulted in HCC cell growth inhibition, apoptosis promotion, cell cycle arrest and metastasis suppression. Mechanically, circSOD2 promoted HCC development by acting as a miR-497-5p sponge and miR-497-5p played a tumor-inhibitory role in HCC cells by targeting ANXA11. Moreover, circSOD2 induced upregulation of ANXA11 expression by interacting with miR-497-5p. Also, the promoting effects of circSOD2 on immune evasion and anti-PD-1 resistance were related to miR-497-5p/ANXA11 axis. This study elucidated the pivotal function of circSOD2 in HCC progression and immunosuppression by mediating miR-497-6p/ANXA11 axis. CircSOD2/miR-497-5p/ANXA11 axis was a novel view of circRNA research in HCC. [ABSTRACT FROM AUTHOR]

Objective: Our study aimed to probe the potential molecular mechanism of long non ⁃ coding RNA (lncRNA) VIM Antisense RNA 1 (VIM⁃AS1) in diabetic retinopathy. Methods: LncRNA VIM⁃AS1, miR⁃497⁃5p and FBXW7 mRNA expressions were determined using qRT⁃PCR. The FBXW7 protein level was also detected using western blotting. The cell viability, migration and apoptosis were evaluated using CCK⁃8 assay, wound healing assay and flow cytometry analysis, respectively. Additionally, the binding relationships among lncRNA VIM⁃AS1, miR⁃497⁃5p and FBXW7 were verified by dual luciferase reporter assaies. Results: LncRNA VIM⁃AS1 and FBXW7 expressions were remarkably reduced in HG⁃treated ARPE⁃19 cells, while miR⁃497⁃5p was upregulated. LncRNA VIM ⁃ AS1 could upregulate the expression of FBXW7 by competitively binding to miR ⁃ 497 ⁃ 5p. LncRNA VIM ⁃ AS1 overexpression promoted cell proliferation and migration, and inhibited cell apoptosis in HG⁃induced ARPE⁃19 cells, while miR⁃497⁃ 5p overexpression abolished the effects of lncRNA VIM⁃AS1 overexpression on HG⁃induced ARPE⁃19 cells. Furthermore, FBXW7 knockdown abrogated the effects of miR⁃497⁃5p inhibition on cell phenotypes of HG⁃treated ARPE⁃19 cells. Conclusion: LncRNA VIM⁃AS1 could promote the proliferation and migration, while inhibited cell apoptosis of HG⁃treated ARPE⁃19 cells by regulation of miR⁃497⁃5p/FBXW7 axis, suggesting that lncRNA VIM⁃AS1 might have great potential as therapeutic target for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background: Centrosomal protein 55 (CEP55) is implicated in the tumorigenesis of bladder cancer (BC) but the detailed molecular mechanisms are unknown. We aim to develop a potential competing endogenous RNA (ceRNA) network related with CEP55 in BC. Methods: We first extracted the expression profiles of RNAs from The Cancer Genome Atlas (TCGA) database and used bioinformatic analysis to establish ceRNAs in BC. Real-time quantity PCR (RT-qPCR) and immunohistochemical analysis were performed to measure CEP55 expression in different bladder cell lines and different grades of cancer. Bioinformatics analysis and luciferase assays were conducted to predict potential binding sites among miR-497-5p, CEP55, parathyroid hormone like hormone (PTHLH) and high mobility group A2 (HMGA2). Tumor xenograft model was used to show the effect of CEP55 3'-UTR on cisplatin therapy. Bioinformatics analysis, luciferase assays, and 5' rapid amplification of cDNA ends (5'RACE) were to explore the function of CEP55 3'-untranslated region (3'-UTR) on targeting miR-497-5p. Western blot and immunofluorescence assays were to detect the epithelial–mesenchymal transition (EMT) induction of CEP55 3'-UTR. Results: CEP55 expression as well as the expression levels of the oncogenic proteins PTHLH and HMGA2 were upregulated in BC cells while miR-497-5p was downregulated. Low miR-497-5p expression and high CEP55 and HMGA2 expression levels were associated with more advanced tumor clinical stage and pathological grade. Overexpression of the CEP55 3'-UTR promoted the proliferation, migration, and invasion of the EJ cell line in vitro and accelerated EJ-derived tumor growth in nude mice, while inhibition of the CEP55 3'-UTR suppressed all of these oncogenic processes. In addition, CEP55 3'-UTR upregulation reduced the cisplatin sensitivity of BC cell lines and xenograft tumors. Bioinformatics analysis, luciferase assays, and 5'RACE suggested that the CEP55 3'-UTR functions as a ceRNA targeting miR-497-5p, leading to miR-497-5p downregulation and disinhibition of PTHLH and HMGA2 expression. Further, CEP55 downregulated miR-497-5p transcription by promoting NF- κ B signaling. In turn, CEP55 3'-UTR ultimately promotes EMT and tumorigenesis by activating P38MAPK and ERK 1/2 pathways. Conclusions: These results suggest that a ceRNA regulatory network involving CEP55 upregulates PTHLH and HMGA2 expression by suppressing endogenous miR-497-5p. We unveiled a novel mechanism of BC metastasis, and could become novel therapeutics targets in BC. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNA (lncRNA) exhibits a crucial role in multiple human malignancies. The expression of lncRNA LINC00511, reportedly, is aberrantly up-regulated in several types of tumors. Our research was aimed at deciphering the role and mechanism of LINC00511 in the progression of cervical cancer (CC). Method: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify the expression levels of LINC00511, miR-497-5p and MAPK1 mRNA in CC tissues and cell lines. Cell counting kit-8 (CCK-8), 5-bromo-2'-deoxyuridine (BrdU) and Transwell assays were conducted for detecting the proliferation, migration and invasion of CC cells. Dual-luciferase reporter gene experiments were performed to verify the targeting relationships amongst LINC00511, miR-497-5p and MAPK1. Besides, MAPK1 expression in CC cells was detected via Western blot after LINC00511 and miR-497-5p were selectively regulated. Results: Up-regulation of LINC00511 expression in CC tissues and cell lines was observed, which was in association with tumor size, clinical stage and lymph node metastasis of the patients. LINC00511 overexpression facilitated the proliferation, migration and invasion of CC cells, while opposite effects were observed after knockdown of LINC00511. Mechanistically, LINC00511 was capable of targeting miR-497-5p and up-regulating MAPK1 expression. Conclusion: LINC00511/miR-497-5p/MAPK1 axis regulates CC progression. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) indicate a repairing prospect to treat spinal cord injury, a major traumatic disease. This study investigated the repair effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on spinal cord injury. BMSCs were collected to extract BMSC-Exos which were identified by different means. The SCI model of rats was established, the motor behavior was scored by BBB field test, and the spinal cord tissues were separated and stained by HE, Nissl, and Tunel, respectively, as well as analyzed to measure inflammatory and oxidative stress responses. PC12 cells were co-cultured with Exos and analyzed by CCK-8 and flow cytometry to measure cell proliferation and apoptosis. BMSC-Exos improved SCI in rats with the recovery of motor function, alleviation of pathological conditions, and reduction of apoptosis, inflammatory responses, and oxidative stress. BMSC-Exos increased miR-497-5p expression, and miR-497-5p overexpression strengthened the protective effect of BMSC-Exos on SCI. miR-497-5p targeted inactivation of TXNIP/NLRP3 pathway. TXNIP saved the repair effect of miR-497-5p-carrying BMSC-Exos on SCI rats. miR-497-5p-carrying BMSC-Exos alleviated apoptosis and induced proliferation of H 2 O 2 -treated PC12 cells. BMSC-Exos promote SCI repair via the miR-497-5p/TXNIP/NLRP3 axis, which may be a target for alleviating SCI-associated nerve damage., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Ethical approval: The present study was approved by the Animal experiments were approved by Wuxi No.8 People’s Hospital Animal Experimental Ethics Committee (Approval number: 2015JN7211). and all procedures complied with the National Institutes of Health Guide for the Use of Laboratory Animals., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Acute myeloid leukemia (AML) is a lethal hematologic malignancy. Chemotherapy resistance results in a dismal survival rate of 1-2 years in older adults with AML. Therefore, novel therapies are urgently required. In this context, microRNA (miRNA)-based treatments remain an untapped strategy in AML. Using patient-derived specimens, we found increased inflammatory cytokines, including interleukin-6 (IL-6) in the serum of older adults with AML, and decreased miR-497-5p in CD34 + leukemic blasts. Target prediction revealed that miR-497-5p could directly target mitogen-activated protein kinase-1 (MAP2K1) mRNA to indirectly target cytokines and the JAK/STAT signaling pathway through the p38-MAPK signaling pathway, potentially inhibiting leukemic growth and overcoming chemoresistance from venetoclax. To improve miRNA delivery and minimize off-target effects, which represent key barriers to clinical translation, we developed liposomes for co-delivery of miR-497-5p and venetoclax. We decorated our liposomes with a peptide targeting CLL1, which is present on 92% of leukemia blasts while being absent in normal hematopoietic cells. This targeted approach demonstrated high efficacy in inhibiting AML growth in mice with minimal toxicity, as well as reduced exposure to chemoresistance. Our findings suggested that anti-CLL1-decorated, miR-497-5p, and venetoclax-loaded liposomes represent a promising novel miRNA-based therapeutic, which should be investigated further as a strategy to reduce venetoclax resistance in AML., Competing Interests: Declaration of interests V.R.B. reports participating in the Safety Monitoring Committee for Protagonist; serving as an associate editor for the journal Current Problems in Cancer; serving as a contributor to BMJ Best Practice; receiving consulting fees from Imugene, Sanofi, and Taiho; receiving research funding (institutional) from MEI Pharma, Actinium Pharmaceutical, Sanofi US Services, Abbvie, Pfizer, Incyte, Jazz, and the National Marrow Donor Program; and receiving drug support (institutional) from Chimerix for a trial., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Long non-coding RNA actin filament-associated protein1-antisense RNA 1 (AFAP1-AS1) was confirmed to be associated with tumorigenesis. However, the role of AFAP1-AS1 in breast cancer was little known. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of AFAP1-AS1, microRNA-497-5p (miR-497-5p), and Septin 2 (SEPT2) in breast cancer tissues and cells. The cell proliferation, migration, and apoptosis were tested by Methylthiazolyldiphenyl-tetrazolium bromide (MTT), Transwell and Flow cytometry assays, respectively. The targeting relationship between genes was predicted by StarBase v.3.0 and confirmed by dual-luciferase reporter assay. Pearson's correlation coefficient was applied to examine the correlation between the two groups. SEPT2 protein expression was evaluated by Western blot. Xenograft models were established to investigate the role of AFAP1-AS1 knockdown in vivo. Results: AFAP1-AS1 was upregulated in breast cancer tissues and cells, and AFAP1-AS1 knockdown could hinder proliferation and migration of breast cancer cells, and contribute to cell apoptosis. MiR-497-5p, which was downregulated in breast cancer, was verified to be a target of AFAP1-AS1 and inversely correlated with AFAP1-AS1 expression. SEPT2, as a target gene of miR-497-5p, was negatively regulated by miR-497-5p and positively correlated with AFAP1-AS1 expression. Importantly, AFAP1-AS1 could upregulate SEPT2 expression by sponging miR-497-5p, and modulate cell progression by regulation of the miR-497-5p/SEPT2 axis in breast cancer. Conclusion: AFAP1-AS1 knockdown repressed the progression of breast cancer cells by sponging miR-497-5p and downregulating SEPT2. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have been proved could regulate many cancers, including prostate cancer (PCa). In this paper, we reconnoitered the roles of circRNA pyruvate dehydrogenase complex component X (circPDHX) in PCa. The circPDHX, microRNA (miR)-497-5p and acyl-CoA synthetase long chain family member 1 (ACSL1) contents were detected by quantitative real-time PCR and Western blot analysis. Cell proliferation was measured by cell counting kit-8 assay, 5-Ethynyl-2′-deoxyuridine assay, and colony formation assay. Cell migration was examined by wound healing assay. The apoptosis was detected by flow cytometry assay. The ELISA kits were applied to quantify the fatty acid metabolites. Furthermore, the interplay between miR-497-5p and circPDHX or ACSL1 was detected by dual-luciferase reporter assay and RIP assay. The role of circPDHX in PCa was supplementary substantiated in vivo. CircPDHX and ACSL1 contents were upregulated, and the miR-497-5p level was downregulated in PCa. CircPDHX deficiency attenuated PCa cell proliferation, migration, and fatty acid metabolites, while intensified cell apoptosis. CircPDHX bound to miR-497-5p to adjust ACSL1. Moreover, miR-497-5p inhibited the PCa progression by regulating ACSL1. In the meantime, circPDHX deficiency repressed PCa tumor growth in vivo. CircPDHX stimulated PCa development via miR-497-5p/ACSL1, which presented a new thought for PCa treatment. • CircPDHX was upregulated in PCa cells. • CircPDHX deficiency attenuated PCa cell progression and tumor growth. • CircPDHX sponged miR-497-5p. • MiR-497-5p targeted ACSL1. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening organ function dysfunction featured by stimulated oxidative stress and inflammatory responses, in which about 40%–60% of sepsis patients are accompanied with cardiac dysfunction. Mesenchymal stem cells (MSCs)-derived exosomes exert critical roles in the treatment of multiple diseases through transferring non-coding RNAs. Circular RNA (circRNA) is a novel form of functional RNAs that involves in the progression of multiple cardiac pathological condition. Nevertheless, the function of MSCs-derived exosomal circRTN4 in sepsis-induced myocardial injury is still obscure. Significantly, FISH assay demonstrated the location of circRTN4 in cytoplasm of cardiomyocytes. The expression of circRTN4 was reduced in the cardiac tissues from caecal ligation and puncture (CLP) rats and LPS-treated cardiomyocytes. CircRTN4 could be delivered to cardiomyocytes cells via MSCs-derived exosomes. The cardiac injury and apoptosis were induced in the CLP rats and the treatment of MSCs-derived exosomal circRTN4 relieved the phenotypes. MSCs-derived exosomal circRTN4 notably suppressed the upregulated ROS level in the CLP rats. The activity of SOD and GSH was repressed in CLP rats, in which MSCs-derived exosomal circRTN4 rescued the activity in the rats. The upregulated IL-1β, IL-6, and TNF-α levels in CLP rats were reduced by the treatment of MSCs-derived exosomal circRTN4. MSCs-derived exosomal circRTN4 improved cell survival and suppressed apoptosis of LPS-treated cardiomyocytes. CircRTN4 direct interact with miR-497-5p to upregulate MG53 expression in cardiomyocytes. MSCs-derived exosomal circRTN4 relieves LPS-stimulated cardiomyocyte damage via targeting miR-497-5p/MG53 axis. Therefore, we determine that MSCs-derived exosomes prevent sepsis-induced myocardial injury by a circRTN4/miR-497-5p/MG53 pathway. Our data provides novel insight into the regulatory mechanism by which MSCs-derived exosomal circRTN4 regulates sepsis-induced myocardial injury. MSCs-derived exosomal circRTN4 may be applied as a promising therapeutic approach for sepsis-induced myocardial injury. • CircRTN4 could be delivered to cardiomyocytes cells via MSCs-derived exosomes. • MSCs-derived exosomal circRTN4 ameliorates MI-induced cardiac dysfunction in rat model. • MSCs-derived exosomal circRTN4 represses LPS-induced cardiomyocyte injury in vitro. • CircRTN4 acts as sponge of miR-497-5p to upregulate MG53 expression in cardiomyocytes. • CircRTN4 relieves LPS-induced cardiomyocyte injury by targeting miR-497-5p/MG53 axis. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the most common lung cancer with a highest mortality rate. MiR-497-5p has been reported as tumor suppressor in many cancers, but the role and mechanism of miR-497-5p in regulating NSCLC progression are still largely unknown in vitro and in vivo. Here, miR-497-5p was significantly downregulated in human NSCLC tissues and cell lines, compared with matched adjacent tissues and normal lung epithelial cell line. Then, miR-497-5p mimic and inhibitor were, respectively, transfected into human NSCLC cells A549 and H460, CCK-8 assay, transwell assay, and flow cytometry were used to detect the capacities of cell proliferation, invasion and apoptosis. MiR-497-5p negatively regulated proliferation and invasion of NSCLC cancer cells. MiR-497-5p was demonstrated to directly bound to 3'-UTR of CX3CL1 mRNA and post-transcriptionally suppressed its expression thus inactivating its downstream oncogenic pathway ERK/AKT. Moreover, transfection with short hairpin RNA (shRNA) against CX3CL1 decreased capacity of cell proliferation and invasion and promoted cell apoptosis in NSCLC cells. In addition, ERK inhibitor U0126 attenuated the promotion effect of miR-497-5p inhibitor on activation of ERK/AKT and cell proliferation and migration. Finally, overexpression of miR-497-5p substantially suppressed activation of the ERK/AKT pathway and tumor growth in tumor-bearing mice in vivo. Taken together, our findings showed that miR-497-5p is downregulated in human NSCLC tissues and cell lines, and it inhibited tumor growth and cell invasion by targeting CX3CL1 gene to inactivate the ERK/AKT pathway in NSCLC cells. [ABSTRACT FROM AUTHOR]

Chemoresistance seriously hinders the treatment efficiency of human cancers, including prostate cancer (PCa). Multiple long noncoding RNAs (lncRNAs) were involved in drug resistance in PCa. We aimed to explore the function of transient receptor potential cation channel subfamily M member 2 (TRPM2) antisense RNA (TRPM2‐AS) in paclitaxel (PTX) resistance in PCa. Our results showed that TRPM2‐AS was increased in PTX‐resistant PCa cells. TRPM2‐AS knockdown accelerated cell apoptosis and inhibited cell proliferation, migration, invasion, and PTX resistance in PTX‐resistant PCa cells. MiR‐497‐5p was bound to TRPM2‐AS and its inhibition reversed the effects of TRPM2‐AS knockdown on cell progression and PTX resistance in PTX‐resistant PCa cells. FOXK1 was identified as a target of miR‐497‐5p and FOXK1 overexpression showed similar effects on cell progression and PTX resistance with miR‐497‐5p inhibition in PTX‐resistant PCa cells. In conclusion, TRPM2‐AS knockdown suppressed cell progression and PTX resistance in PTX‐resistant PCa cells by miR‐497‐5p/FOXK1 axis. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play crucial roles in the development of diabetic nephropathy (DN). Here, we explored the activity and mechanism of MIR503 host gene (MIR503HG) in high glucose (HG)-evoked cytotoxicity in HK-2 cells. MIR503HG, microRNA (miR)-497-5p, and C–C motif chemokine ligand 19 (CCL19) were quantified by quantitative real-time PCR (qRT-PCR) and western blot. The direct relationship between miR-497-5p and MIR503HG or CCL19 was confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Cell viability and apoptosis were evaluated by XTT assay and flow cytometry, respectively. Our data showed that MIR503HG was overexpressed in HG-stimulated HK-2 cells. Knockdown of MIR503HG alleviated HG-evoked cell apoptosis, inflammation, and fibrosis in HK-2 cells. Mechanistically, MIR503HG regulated miR-497-5p expression via a binding site. MIR503HG depletion reduced HG-evoked cell apoptosis, inflammation, and fibrosis in HK-2 cells by up-regulating miR-497-5p. Moreover, miR-497-5p directly targeted and suppressed CCL19. MiR-497-5p-mediated suppression of CCL19 relieved HG-induced cell apoptosis, inflammation, and fibrosis in HK-2 cells. Furthermore, MIR503HG regulated CCL19 expression via miR-497-5p competition. Our findings identify a new MIR503HG/miR-497-5p/CCL19 network in the regulating HG-evoked cell apoptosis, inflammation, and fibrosis in HK-2 cells. [ABSTRACT FROM AUTHOR]

The cause of posterior capsular opacification (PCO) is the dysfunction of lens epithelial cells (LECs). Circular RNA (circRNA) was found to regulate cell biological functions, including LECs. However, the role of circ-GGA3 in PCO formation is unclear. Quantitative real-time PCR was used to measure the expression of circ-GGA3, miR-497-5p and SMAD4. Cell proliferation, invasion and migration were determined via MTT assay, EdU staining, transwell assay and wound healing assay. The protein expression of epithelial-mesenchymal transition (EMT) markers, fibrosis markers, TGF-β/SMAD pathway markers and SMAD4 were determined by western blot assay. The interaction between miR-497-5p and circ-GGA3 or SMAD4 was confirmed using dual-luciferase reporter assay. Circ-GGA3 was highly expressed in PCO patients, and its silencing inhibited the proliferation, invasion, migration, EMT process and fibrosis of TGF-β2-induced LECs. Circ-GGA3 could sponge miR-497-5p to regulate SMAD4. Further experiments revealed that miR-497-5p inhibitor recovered the negative regulation of circ-GGA3 knockdown on the biological functions of TGF-β2-induced LECs, and SMAD4 overexpression also abolished the suppressive effect of miR-497-5p. In addition, circ-GGA3/miR-497-5p/SMAD4 axis could activate the TGF-β/SMAD pathway. Our results indicated that circ-GGA3 could enhance the biological functions of LECs, suggesting that circ-GGA3 might be a potential target for PCO therapy. • Circ-GGA3 silencing inhibits the viability, migration, invasion and EMT process of TGF-β2-induced LECs. • Circ-GGA3 serves as miR-497-5p sponge. • MiR-497-5p targets SMAD4. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a major kind of head and neck epithelial carcinoma. Increasing evidences reveal that long noncoding RNAs are considered as vital regulators in tumorigenesis and progression. Although previous studies have found that cancer susceptibility candidate 9 (CASC9) highly expresses in NPC, the underlying mechanisms need to be further studied. In this study, we found that CASC9 was overexpressed and associated with worse prognosis in NPC. CASC9 knockdown significantly inhibited the cell proliferation, migration and invasion in vitro and enhanced the sensitivity of tumor cells to cisplatin and paclitaxel. Mechanism research confirmed CASC9 regulated the malignant biological behavior of nasopharyngeal carcinoma cells by targeting miR-497-5p/Wnt3a/β-catenin signaling pathway. The present study might provide a novel mechanism for tumorigenesis and progression of NPC and contribute to the development of an effective molecular target therapy. [ABSTRACT FROM AUTHOR]

It is known that miRNA mediates the formation of osteogenesis, but the mechanism by which miRNA let-7a-5p regulates osteogenesis in osteoporosis (OP) is not yet understood. This paper aims to probe into the regulatory mechanism of miRNA let-7a-5p in the development of OP. Fresh femoral trabecular bones of patients with osteoporotic fracture (OP group, n = 25) and non-OP osteoarthritis (Non-OP group, n = 23) who underwent hip replacement in our hospital from December 2016 to December 2019 were collected. The expression and protein levels of miRNA let-7a-5p and V-AKT murine thymoma viral oncogene homolog 3 (RNA KCNQ1OT1) were detected. C2C12 cells were purchased and osteogenic differentiation model was constructed by BMP2 induction. After miRNA let-7a-5p up-regulation or down-regulation by transfection of corresponding mimics and inhibitors, the impacts of miRNA let-7a-5p and RNA KCNQ1OT1 on osteogenic differentiation-related factors (OC, ALP, COL1A1) in C2C12 cells were analyzed. The determination of targeting correlation of miRNA let-7a-5p with RNA KCNQ1OT1 was performed by dual-luciferase reporter (DLR). In OP samples, miRNA let-7a-5p was notably declined while RNA KCNQ1OT1 were remarkably up-regulated. MiRNA let-7a-5p reduced in C2C12 cells as BMP2 treatment proceeded. MiRNA let-7a-5p up-regulation or RNA KCNQ1OT1 down-regulation increased OC, ALP, COL1A1 levels and ALP activity. RNA KCNQ1OT1 was directly targeted to miR-497-5p. RNA KCNQ1OT1 up-regulation weakened the promoting effect of miRNA let-7a-5p up-regulation on osteoblast differentiation. MiRNA let-7a-5p up-regulation can target to reduce RNA KCNQ1OT1 and promote osteoblast differentiation, thereby improving the development of osteoporosis. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are key regulators in hepatocellular carcinoma (HCC) tumorigenesis and development, yet it is unclear whether circ-CCND1 participates in regulating HCC progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for detecting the expressions of circ-CCND1, microRNA (miR) -497-5p, and high mobility group AT-hook 2 (HMGA2) mRNA in HCC tissues and cell lines. Subcellular fractionation assay was used to analyze the localization of circ-CCND1 in HCC cell lines. Loss-of-function experiments were conducted to examine the effects of circ-CCND1 on HCC cell proliferation, migration, and invasion. Dual-luciferase reporter gene assay was employed for detecting the targeting relationships of circ-CCND1 and miR-497-5p, as well as miR-497-5p and HMGA2, respectively. Western blot was used to detect the regulatory functions of circ-CCND1 and miR-497-5p on HMGA1 expression at protein level. Circ-CCND1 and HMGA2 expressions in HCC were significantly up-regulated and miR-497-5p expression was markedly decreased. High circ-CCND1 expression was associated with relatively large tumor size and lymph node metastasis in HCC patients. In addition, circ-CCND1 was mainly distributed in the cytoplasm of HCC cells. Functionally, knockdown of circ-CCND1 remarkably suppressed HCC cell proliferation, migration, and invasion. Mechanistically, miR-497-5p was a direct target of circ-CCND1 and miR-497-5p specifically modulated HMGA2 expression. Furthermore, miR-497-5p inhibitors and or HMGA2 overexpression partially counteracted the suppressing effect induced by si-circ-CCND1 on the malignant phenotype of HCC cells. Circ-CCND1 plays a cancer-promoting role in HCC by modulating the miR-497-5p/HMGA2 axis. Therefore, targeting circ-CCND1 is likely to be a promising therapeutic strategy for HCC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a major kind of head and neck epithelial carcinoma. Increasing evidences reveal that long noncoding RNAs are considered as vital regulators in tumorigenesis and progression. Although previous studies have found that cancer susceptibility candidate 9 (CASC9) highly expresses in NPC, the underlying mechanisms need to be further studied. In this study, we found that CASC9 was overexpressed and associated with worse prognosis in NPC. CASC9 knockdown significantly inhibited the cell proliferation, migration and invasion in vitro and enhanced the sensitivity of tumor cells to cisplatin and paclitaxel. Mechanism research confirmed CASC9 regulated the malignant biological behavior of nasopharyngeal carcinoma cells by targeting miR-497-5p/Wnt3a/β-catenin signaling pathway. The present study might provide a novel mechanism for tumorigenesis and progression of NPC and contribute to the development of an effective molecular target therapy.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) has been reported to participate in the regulation of various nervous system disorders. Bupivacaine (BV), a commonly used local anesthetic, could generate neurotoxicity in neurons. This work intended to investigate the role and specific mechanism of SNHG12 in BV-induced neurotoxicity. In this study, we established an in vitro cell model of BV-induced neurotoxicity by exposing human neuroblastoma cells (SH-SY5Y) to BV. It was found that SNHG12 and NLRX1 levels were gradually downregulated, while miR-497–5p enrichment was upregulated accordingly with the increase of BV concentration. As indicated by functional assays, SNHG12 overexpression promoted cell viability but inhibited cell apoptosis and oxidative stress in BV-treated SH-SY5Y cells. In addition, it was identified that SNHG12 directly targeted miR-497–5p and attenuated BV-induced neurotoxicity via interaction with miR-497–5p. Besides, it was confirmed that SNHG12 could upregulate NLRX1 expression by absorbing miR-497–5p. Moreover, miR-497–5p decreased cell viability and induced cell apoptosis and oxidative stress, which was partly reversed by NLRX1 upregulation. In conclusion, our findings indicated that SNHG12 might relieve BV-associated neurotoxicity by upregulating NLRX1 via miR-497–5p in vitro, providing novel clues and biomarkers for the treatment and prevention of BV-associated neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: This research aims to investigate the expression and biological roles of miR-497-5p in gastric cancer (GC), and its possible mechanisms. Methods: Real Time Quantitative PCR (RT-qPCR) was performed to detect miR-497-5p in GC and normal tissues, as well as GC cell lines versus normal gastric mucosal cells (GES-1). The effects of miR-497-5p overexpression on proliferation were measured by the cell counting kit-8 (CCK8) assay and ethidium bromide (EdU) assay. Flow cytometry was used to assess the cell cycle. The migration and invasion were evaluated by scratch assay and Transwell assay, respectively. Gene targets of miR-497-5p were predicted using "multiMiR" R package combined with mirTarPathway database. And then luciferase reporter experiment was used to evaluate the activity of ERBB2 by miR-497-5p mimics in GC cell line. Besides, functional experiments were performed to verify the impact of miR-497-5p /ERBB2 on phenotypes of GC cells. Results: Compared with the normal tissues and mucosal cells, miR-497-5p was reduced in GC tissues and GC cell lines. miR-497-5p significantly decreased proliferation, migration, and invasion capacity, with an elevated apoptosis ratio of gastric cancer cells. Bioinformatics indicated that ERBB2 might be the potential target of miR-497-5p Dual-luciferase reporter experiments showed it adversely regulated ERBB2 3'UTR luciferase activity. The expression of ERBB2 in GC tissues and cells is significantly higher compared to normal tissues and cells. Over-expression of ERBB2 in gastric cancer cells significantly reduced miR-497-5p's inhibitory effect on the malignant behavior of GC cells. Conclusion: miR-497-5p was significantly down-regulated in GC tissues and cells, which inhibited the malignant features of GC cells by targeting ERBB2., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The impairment of endothelial cells triggered by oxidized low-density lipoprotein (ox-LDL) stands as a critical event in the advancement of atherosclerosis (AS). MiR-497-5p has been recognized as a potential predictor for AS, but its precise involvement in ox-LDL-induced endothelial cell dysfunction remains to be elucidated., Methods: An in vitro AS cell model was established by exposing human umbilical vein endothelial cells (HUVECs) to 100 μg/mL ox-LDL for 24 h. The assessment of endothelial cell function included evaluating cell viability, caspase-3 activity, inflammatory factors, and oxidative markers. Molecular mechanisms were elucidated through quantitative real-time PCR, Western blot analysis, and luciferase reporter assays., Results: Our investigation revealed that exposure to ox-LDL led to an upregulation in miR-497-5p and p-p38 levels, while downregulating the expression of vascular endothelial growth factor A (VEGFA) and phosphorylated (p)-endothelial nitric oxide synthase ( p -eNOS) in HUVECs. Ox-LDL exposure resulted in decreased cell viability and angiogenic capacity, coupled with increased apoptosis, inflammation, and oxidative stress in HUVECs, partially mediated by the upregulation of miR-497-5p. We confirmed VEGFA as a direct target of miR-497-5p. Interfering with VEGFA expression significantly reversed the effects mediated by miR-497-5p silencing in HUVECs exposed to ox-LDL., Conclusions: In summary, our findings demonstrate that miR-497-5p exacerbates ox-LDL-induced dysfunction in HUVECs through the activation of the p38/MAPK pathway, mediated by the targeting of VEGFA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Epithelial-mesenchymal transition (EMT) is a vital pathological feature of silica-induced pulmonary fibrosis. However, whether circRNA is involved in the process remains unclear. The present study aimed to investigate the role of circPVT1 in the silica-induced EMT and the underlying mechanisms. We found that an elevated expression of circPVT1 promoted EMT and enhanced the migratory capacity of silica-treated epithelial cells. The isolation of cytoplasmic and nuclear separation assay showed that circPVT1 was predominantly expressed in the cytoplasm. RNA immunoprecipitation assay and RNA pull-down experiment indicated that cytoplasmic-localized circPVT1 was capable of binding to miR-497-5p. Furthermore, we found that miR-497-5p attenuated the silica-induced EMT process by targeting transcription factor 3 (TCF3), an E-cadherin transcriptional repressor, in the silica-treated epithelial cells. Collectively, these results reveal a novel role of the circPVT1 /miR-497-5p/TCF3 axis in the silica-induced EMT process in lung epithelial cells. Once validated, this finding may provide a potential theoretical basis for the development of interventions and treatments for pulmonary fibrosis.

Background: Cervical cancer is prevalent throughout the world, and microRNA-497-5p (miR-497-5p) plays an important role in its development. However, the specific mechanism by which miR-497-5p targets the transferrin receptor (TFRC) during cervical cancer development has not been clarified., Objectives: The aim of the study was to unravel TFRC expression and its role in cervical cancer cells, as well as the impact of the miR-497-5p/TFRC axis on cervical cancer cells., Material and Methods: The target mRNA was determined through differential analysis, followed by the evaluation of its impact on survival and clinical staging. Then, quantitative real-time polymerase chain reaction (qPCR) was conducted to analyze the TFRC mRNA level in cervical cancer cells and normal cervical epithelial cells. Western blot (WB) was utilized to examine the expression levels of TFRC, cleaved caspase-3, cleaved caspase-9, and epithelial-mesenchymal transition (EMT)-related proteins. The miRNAs upstream of the target mRNA were predicted, and Pearson correlation analysis was performed, followed by the validation through the dual-luciferase reporter assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were performed to analyze cancer cell viability, followed by a transwell assay aimed at measuring cell migratory and invasive abilities. Finally, flow cytometry was conducted to examine cell apoptosis and cell cycle., Results: The transferrin receptor was significantly increased in cervical cancer cells and positively associated with clinical T and N stages. Silencing TFRC could constrain cell proliferative, migratory and invasive abilities, arrest the cell cycle and facilitate cell apoptosis in cervical cancer cells. The bioinformatics analysis showed a significantly negative correlation between miR-497-5p and TFRC in cervical cancer. Moreover, upregulated miR-497-5p hampered cervical cancer progression and decreased TFRC expression. The overexpression of TFRC reversed the suppressive impact of miR-497-5p overexpression on cervical cancer progression., Conclusions: The modulatory role of the miR-497-5p/TFRC axis was confirmed in cervical cancer cells. This axis may present a new avenue for the diagnosis of cervical cancer and provide a novel target for cervical cancer treatment.

Hepatocellular Carcinoma (HCC), also called hepatocellular cancer, has emerged as a highly prevalent malignancy globally. By binding to specific RNA via one or more spherical RNA Domains (RBDs) or RNA Motifs (RBMs), RNA Binding Proteins (RBPs) can affect RNA modification, splicing, localization, translation, and stability. This paper builds on previous research by further investigating the impact of RBM12 on LC progression. In order to determine the effect of RBM12 expression on the prognosis of patients with hepatocellular cancer, we first investigated its expression in liver cancer cells (LCC) and tissues. The effect of RBM12 on the malignant biological behavior of LCC was subsequently detected using cytological experiments. To explore the upstream mechanism affecting RBM12, we predicted the miRNA targeting RBM12. According to the database, miR-497–5p was the best candidate gene. The double Luciferase reporter gene experiment was executed to validate the bounding of miR-497–5p with RBM12. According to the cytological experiments, a high RBM12 expression promoted the propagation, migration, and invasion of LCC and impeded liver cancer cell apoptosis. By secreting TGF-β1, RBM12 could induce the EMT process. The miR-497–5p expression is suppressed in hepatocellular cancer. As shown by the CCK8, plate cloning, Transwell, EDU, and other experiments, miR-497–5p suppressed RBM12 expression and tumor growth. The double Luciferase reporter gene system was utilized to verify the combination of miR-497–5p and RBM12. The CPNE1 is a downstream gene regulated by RBM12. A high CPNE1 expression was exhibited in LCC and tissues. The CPNE1 is essential in the process where RBM12 promotes the incidence and progression of liver cancer. By elucidating the exact molecular mechanism through which RBM12 promotes the initiation and progression of LC, thus, the current investigation provides some reference for the clinical management of LC. • RBM12 expression stimulates liver cancer cell abilities while suppressing apoptosis. • MiR-497–5p represses RBM12 expression and tumor growth in liver cancer. • CPNE1 is a downstream gene regulated by RBM12, mediating liver cancer growth. • Lenvatinib inhibits RBM12 expression, suggesting therapeutic potential in liver cancer. • Insights into RBM12/CPNE1 pathway provide potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is a disease that primarily affects adolescents with skeletal immaturity. LncRNAs are abnormally expressed and correlated with osteosarcoma patients' prognosis. We identified aberrant expression of LncRNA SNHG25 (small nucleolar RNA host gene 25) in osteosarcoma and analyzed the molecular mechanisms by which it regulates osteosarcoma progression., Methods: The expression levels of SNHG25 in tumour specimens and cells were measured by RTqPCR. Loss-of-function assays were conducted to investigate the functional role of SNHG25 in vitro and in vivo . Bioinformatic predictions, dual-luciferase reporter assays, and western blotting were performed to explore the possible underlying mechanisms., Results: SNHG25 was highly expressed in osteosarcoma cells and tissues. The Kaplan-Meier curve showed that the survival rate of patients with high SNHG25 expression was significantly lower than those with low SNHG25 expression. Functional studies have indicated that inhibition of SNHG25 suppresses cell proliferation, migration, and invasion, while promoting apoptosis. SNHG25 knockdown suppresses osteosarcoma tumour growth in vivo . SNHG25 functions as a sponge for miR-497-5p in osteosarcoma cells. The level of SNHG25 was negatively correlated with that of miR-497-5p. The proliferation, invasion, and migration of osteosarcoma cells were restored by transfection of the miR-497-5p inhibitor in the SNHG25 knockdown group., Conclusion: SNHG25 was determined to function as an oncogene by promoting osteosarcoma cell proliferation, invasion, and migration through the miR-497-5p/SOX4 axis. Upregulation of SNHG25 expression indicated poor prognosis in patients with osteosarcoma, which showed that SNHG25 may serve as a potential therapeutic target and prognostic biomarker in osteosarcoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)