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Objective: To investigate the expression of microRNA-1290 (miR-1290) and miR-134 in helicobacter pylori (Hp) positive gastric cancer tissues and their relationship with tumor proliferation genes, invasion genes and prognosis. Methods: 126 patients with gastric cancer who were admitted to Three Gorges Hospital Affiliated to Chongqing University from January 2016 to January 2017 were selected as the study subjects. According to the Hp detection results, they were divided into Hp-positive gastric cancer group (n=84) and Hp-negative gastric cancer group (n=42), and 60 patients with chronic gastritis in the same period were taken as the control group. The expression of miR-1290, miR-134, proliferation genes [phosphatidylinositol 3 catalytic subunit A (PIK3CA), C-myc oncogene (c-myc)] and invasion genes [basic helix helix transcription factor (Twist), N cadherin (N-cad)] were detected by real-time fluorescence quantitative polymerase chain reaction. Pearson correlation analysis of the correlation between miR-1290, miR-134 and the expression of PIK3CA, c-myc and invasive genes Twist and N-cad in Hp-positive gastric cancer tissues. The expression differences of miR-1290 and miR-134 in patients with Hp positive gastric cancer with different clinicopathological characteristics were compared. Kaplan-Meier survival curve was used to evaluate the relationship between the expression of miR-1290 and miR-134 and the survival and prognosis of Hp-positive patients with gastric cancer. Results: The expression of miR-1290 in cancer tissues of the HP-positive gastric cancer group was higher than that of the HP-negative gastric cancer group and control group, while the expression of miR-134 was lower than that of the HP-negative gastric cancer group and control group, with statistical significance (P<0.05). The expression of miR-1290 of the HP-positive gastric cancer tissues were positively correlated with the expressions of proliferating genes PIK3CA and c-myc, invasion genes Twist and N-cad mRNA (r=0.620～0.725, all P<0.05), and miR-134 was negatively correlated with the expressions of proliferating genes PIK3CA and c-myc, and invasion genes Twist and N-cad mRNA (r=-0.670 ～-0.784, all P<0.05). There were statistically significant differences in the expression of miR-1290 and miR-134 in cancer tissues of patients with different TNM stages, depth of invasion and lymph node metastasis of HP-positive gastric cancer (all P<0.05). The 5-year overall survival rates of patients with HP-positive gastric cancer were 48.78% (20/41) and 75.61% (31/41) of the high-expression group and low-expression group of miR-1290, respectively. The cumulative survival of patients with miR-1290 high expression group was significantly lower than that of patients with miR-1290 low expression group (Log rank x²=6.366, P= 0.012). The 5-year overall survival rates were 42.86%(18/42) and 82.50% (33/40) in the low-expression group and high-expression group of miR-134, respectively. The cumulative survival of miR-134 low expression group was significantly lower than that of miR-134 high expression group (Log rank x² =10.640, P=0.001). Conclusion: The increased expression of miR-1290 and decreased expression of miR-134 in HP-positive gastric cancer tissues may lead to malignant progression and poor prognosis by promoting the expression of tumor proliferation and invasion genes. [ABSTRACT FROM AUTHOR]

The mechanism of hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) upregulation and its function in head and neck squamous cell carcinoma (HNSCC) remains obscure. Herein, the expression and function of HPRT1 and the mechanism underlying its upregulation in HNSCC were explored. Firstly, the expression of HPRT1 and its prognostic values were simultaneously validated using bioinformatic analysis and quantitative real-time PCR (qRT-PCR), and immunohistochemistry staining with local HNSCC samples. The effects of HPRT1 knockdown on proliferation and invasion of HNSCC cells were detected using cell counting kit-8 (CCK-8), plate clone formation, Transwell invasion, nude mouse xenograft model assays. Moreover, the miRNA targeting HPRT1 was validated using dual-luciferase report assay, qRT-PCR and Western blot analysis. The functions of miRNA targeting HPRT1 and its dependence on HPRT1 were further investigated in HNSCC. The results indicated that HPRT1 was highly expressed in HNSCC tissues and cells, which positively correlated with advanced tumor progression and predicted poor prognosis in patients with HNSCC. HPRT1 knockdown markedly inhibited proliferation and invasion of HNSCC cells both in vitro and in vivo. MiR-125b-5p, which was downregulated and positively correlated with a favorable outcome for patients, directly targeted and downregulated HPRT1 expression, and subsequently suppressed cell proliferation and invasion in HNSCC. Collectively, the present study demonstrates that HPRT1 upregulation, at least partially caused by miR-125b-5p downregulation, could promote the malignant progression of HNSCC, highlighting the potential application of the miR-125b-5p/HPRT1 axis as a novel indicator and target in the diagnosis and treatment of HNSCC.

lncRNA DSCR8 (Down syndrome critical region 8) is involved in progression of many cancers, but its specific role in gastric cancer (GC) is still unclear. Here, qRT-PCR detected upregulated expression of DSCR8 and Cdc42 and downregulated expression of miR-137 in GC. The protein expression level of Cdc42 in GC was upregulated as tested by western blot. Statistical analysis showed that DSCR8 was closely associated with some malignant clinicopathological features (such as tumor size, metastasis, and stage) in GC patients. Fluorescence in situ hybridization showed that DSCR8 was localized in the nucleus and cytoplasm. Dual-luciferase reporter gene, RNA immunoprecipitation, and biotin pull-down assays showed that DSCR8 could bind to miR-137 could bind to Cdc42. In vitro and in vivo assays showed that DSCR8 could promote proliferation, invasion, and the cycle of GC cells and inhibit cell apoptosis. In addition, a rescue experiment showed that DSCR8 regulated progression of GC cells via miR-137. Furthermore, DSCR8 regulated Cdc42 in GC cells by inhibiting miR-137. Taken together, these data indicated that DSCR8 could adsorb miR-137 to reduce its inhibitory effect on Cdc42 expression, thereby promoting the progression of GC cells and regulating the cell cycle. These results provide a novel direction for DSCR8 as a target of GC.

The underlying mechanisms of E2F5 upregulation and its pro-tumor functions have not been elucidated in gastric cancer (GC). Here, the expression, prognostic value, mutation status, and promoter methylation of E2F5 were evaluated. The effects of E2F5 depletion on cell proliferation and invasion in GC, were also assessed through in vitro experiments. Additionally, gene set enrichment analysis (GSEA) was applied to analyze the potential downstream regulator of E2F5. The study also assessed the correlation and transcription regulation between E2F5 and UBE2T. Finally, the roles of UBE2T in E2F5-related pro-tumor functions were examined. The findings revealed that E2F5 was upregulated and showed remarkable association with pathological variables and prognosis. Hypomethylation of the E2F5 promoter predicted poor prognosis and partially caused E2F5 upregulation in GC. E2F5 knockdown significantly inhibited the proliferation and invasion of GC cells. E2F5 had a significant positive correlation with UBE2T in GC. Mechanistically, E2F5 promoted UBE2T transcription and UBE2T overexpression reversed the effects of E2F5 depletion on the proliferation and invasion of cells in GC. Taken together, this study originally confirmed the upregulation of E2F5 in GC, revealed that E2F5 can directly upregulate UBE2T transcription, and subsequently promote the malignant progression, which highlights that the E2F5/UBE2T axis can potentially be used in the diagnosis and treatment of GC. [ABSTRACT FROM AUTHOR]

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Shihao Zhang,* Jiansheng Liu,* Taiwen Yuan, Huiyu Liu, Chengwei Wan, Yonghong Le Department of Respiratory and Critical Care Medicine, Ganzhou People’s Hospital, Ganzhou 341000, Jiangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong LeDepartment of Respiratory and Critical Care Medicine, Ganzhou People’s Hospital, No. 17, Hongqi Avenue, Zhanggong District, Ganzhou 341000, Jiangxi, People’s Republic of ChinaTel/Fax +8613879769189Email Yonghongle3112@163.comBackground: Non-small cell lung cancer (NSCLC) seriously endangers human health. Circular RNAs (circRNAs) regulate diverse types of cancers, including NSCLC. This study investigated the possible mechanism of circ0001313 in NSCLC.Materials and Methods: Circ0001313 expression in NSCLC tissues was measured, and its correlation with clinicopathological features was analyzed. The binding relationships among circ0001313, microRNA (miR)-452 and HMGB3 were tested. The gain and loss of functions were performed to examine NSCLC cell malignant behaviors. After HMGB3 overexpression, ERK/MAPK pathway-related protein levels were detected. Subsequently, the rescue experiment was further performed using an ERK/MAPK pathway inhibitor PD98059.Results: Abnormally elevated circ0001313 and decreased miR-452 in NSCLC cells were observed. Circ0001313 silencing or miR-452 overexpression significantly reduced NSCLC cell proliferation and invasion. Circ0001313 competitively bound to miR-452 to upregulate HMGB3, thus promoting NSCLC cell growth. HMGB3 overexpression activated the ERK/MAPK pathway to contribute to NSCLC development.Conclusion: We highlighted that silencing of circ0001313 blunted the ERK/MAPK pathway via the miR-452/HMGB3 axis, thereby inhibiting NSCLC cell proliferation and invasion.Keywords: non-small cell lung cancer, circular RNA 0001313, microRNA-452, HMGB3, ERK/MAPK pathway, proliferation and invasion

The interaction between the TEAD4 expression and the proliferation and invasion of cervical squamous cell carcinoma (CSCC) is investigated. The Imunohistochemistry MaxVision and the Optical Denstity analysis were used to detect the expression of TEAD4 in CSCC tissues. Overexpression of TEAD4 gene in SiHa cells was acquired by transfecting the expressing plasmid (pCMV3-TEAD4). The expressions of protein levels in cells were assessed by Western blotting. The proliferation and invasive capacity of cervical squamous carcinoma cells were evaluated by CCK8 assay and Transwell Chamber assay, respectively. TEDAD4 showed a significantly higher expression level in CSCC (0.179 ± 0.00743) than that in normal cervical epithelia(0.058± 0.00092, P <0.001). TEAD4 expression was related to the lymph node metastasis, the vascular invasion and the parametrial involvement of CSCC, but not related to the patients' age, the tumor size and the differentiation degree of CSCC.TEAD4 expression was positively correlated to the ex-pression of MMP9 (r =0.394, P<0.01). The proliferation and invasive capacity of SiHa cells with TEAD4 gene transfection was significantly increased in comparison with the cancer cells without gene transfection. TEAD4 gene transfection led to an increase of P-ERK and MMP9 expression in SiHa cells. The specific inhibitor of ERK1/2 signaling, U0126, could inhibit TEAD4-mediated up-regulation of MMP9 in SiHa cells. EAD4 showed a high expression level in CSCC and promoted the caner proliferation and invasion, and this mechanism may be related to the TEAD4-mediated activation of ERK1/2-MMP9 signal pathway. [ABSTRACT FROM AUTHOR]

To investigate how long non-coding RNAs DUXAP8 (LncRNA DUXAP8) influence the cell proliferation and invasion of non-small-cell lung cancer (NSCLC), we detected the expression levels of LncRNA DUXAP8 in lung cancer (LC) tissues, 4 LC-related cell lines (A549, SPC-A1, SK-MES-1 and NCI-H1299) and normal lung tissues via quantitative real-time PCR (qRT-PCR). Compared with normal lung tissue, LncRNA DUXAP8 was significantly up-regulated in NSCLC, especially in stage III / IV and diameter ≥ 3cm of lung cancer. Among 4 lung cancer cell lines, LncRNA DUXAP8 in A549 cells was the highest (P

The pathogenesis of papillary thyroid cancer (PTC), the most common type of thyroid cancer, is not yet fully understood. This limits the therapeutic options for approximately 7% of invasive PTC patients. The critical role of AUF1 in the progression of thyroid cancer was first reported in 2009, however, its molecular mechanism remained unclear. Our study used CRISPR/Cas 9 system to knockdown AUF1 in IHH4 and TPC1 cells. We noticed that the expression of TRIM58 and ZBTB2 were increased in the AUF1 knockdown IHH4 and TPC1 cells. When TRIM58 and ZBTB2 were inhibited by small hairpin RNAs (shRNAs) against TRIM58 (shTRIM58) and ZBTB2 (shZBTB2), respectively, the proliferation, migration, and invasion ability of the AUF1-knockdown IHH4 and TPC1 cells were increased. In addition, two ZBTB2 binding sites (-719~-709 and -677~-668) on TRIM58 promoter and two AUF1 binding sites (1250-1256 and 1258-1265) on ZBTB2 3’-UTR were identified. These results suggested that AUF1 affecting thyroid cancer cells via regulating the expression of ZBTB2 and TRIM58.

The pathogenesis of papillary thyroid cancer (PTC), the most common type of thyroid cancer, is not yet fully understood. This limits the therapeutic options for approximately 7% of invasive PTC patients. The critical role of AUF1 in the progression of thyroid cancer was first reported in 2009, however, its molecular mechanism remained unclear. Our study used CRISPR/Cas 9 system to knockdown AUF1 in IHH4 and TPC1 cells. We noticed that the expression of TRIM58 and ZBTB2 were increased in the AUF1 knockdown IHH4 and TPC1 cells. When TRIM58 and ZBTB2 were inhibited by small hairpin RNAs (shRNAs) against TRIM58 (shTRIM58) and ZBTB2 (shZBTB2), respectively, the proliferation, migration, and invasion ability of the AUF1-knockdown IHH4 and TPC1 cells were increased. In addition, two ZBTB2 binding sites (-719~-709 and -677~-668) on TRIM58 promoter and two AUF1 binding sites (1250-1256 and 1258-1265) on ZBTB2 3'-UTR were identified. These results suggested that AUF1 affecting thyroid cancer cells via regulating the expression of ZBTB2 and TRIM58. [ABSTRACT FROM AUTHOR]

Most patients with multiple myeloma (MM) will eventually relapse and current treatments have limited effect. Herein, we demonstrate that succinate dehydrogenase subunit A (SDHA) was low expressed in MM patients, and patients with SDHA relatively high expression had long overall survival and progression-free survival. Furthermore, SDHA high expression inhibited proliferation and invasion in MM cell lines and enhanced the anti-tumor and synergistic effect of chemotherapeutics. More importantly, chidamide was proved effective in MM by targeting SDHA, and expression of SDHA was increased by chidamide through acetylating H3K27 site of SDHA. Collectively, high expression of SDHA, which was regulated by histone acetylation and targeted by chidamide, might become a good prognostic factor of MM patients.

Most patients with multiple myeloma (MM) will eventually relapse and current treatments have limited effect. Herein, we demonstrate that succinate dehydrogenase subunit A (SDHA) was low expressed in MM patients, and patients with SDHA relatively high expression had long overall survival and progression-free survival. Furthermore, SDHA high expression inhibited proliferation and invasion in MM cell lines and enhanced the anti-tumor and synergistic effect of chemotherapeutics. More importantly, chidamide was proved effective in MM by targeting SDHA, and expression of SDHA was increased by chidamide through acetylating H3K27 site of SDHA. Collectively, high expression of SDHA, which was regulated by histone acetylation and targeted by chidamide, might become a good prognostic factor of MM patients. [ABSTRACT FROM AUTHOR]

Transmembrane protein 98 (TMEM98) is a recently discovered gene, the inhibition of which has preliminarily been demonstrated to inhibit progression of several solid cancers in vitro. However, its involvement in tumorigenesis of gastric cancer (GC) has not been reported. Here, we aimed to explore the expression of TMEM98 in GC tissues and cell lines and to determine the role of TMEM98 in GC cell proliferation and invasion. TMEM98 was significantly upregulated in GC tissues, which was associated with low survival rate of GC patients. Interestingly, GC cell proliferation and invasion were promoted by TMEM98 messenger RNA (mRNA) upregulation and inhibited by TMEM98 mRNA downregulation, but not affected by TMEM98 protein. Using RNA‐binding protein immunoprecipitation assay and RNA pull‐down assay, we demonstrated that TMEM98 mRNA could directly bind with and upregulate nuclear factor 90 (NF90). Similarly, NF90 protein could not only enhance the stability of TMEM98 mRNA but antagonize the suppressive effect of TMEM98‐small interfering RNA on proliferation and invasion in MKN‐45 cells. Moreover, RNA pull‐down assay, with wild‐type (WT) and binding‐site‐mutated biotinylated TMEM98 mRNA transcripts, demonstrated that WT TMEM98 mRNA bound with NF90 protein through an 8‐nt motif at the last exon, but the motif mutation abolished the capacity of TMEM98 mRNA binding to NF90 protein. Furthermore, overexpression of the WT last exon of TMEM98 increased NF90 expression and cell proliferation/invasion expectedly, but overexpression of the mutated last exon had no obvious effect. In conclusion, TMEM98 mRNA enhanced the proliferation and invasion of GC cells by interacting with the NF90 protein. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) belongs to the high‐grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non‐coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435‐2 Host Gene (MIR4435‐2HG) in GBM. Data from GEPIA database showed that MIR4435‐2HG was up‐regulated in GBM tissues and high expression of MIR4435‐2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up‐regulation of MIR4435‐2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435‐2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435‐2HG overexpression driven GBM progression. Furthermore, MIR44435‐2HG was found to sponge miR‐1224‐5p and suppress miR‐1224‐5p expression; overexpression of miR‐1224‐5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435‐2HG overexpression. In a subsequent study, miR‐1224‐5p was found to target transforming growth factor‐beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR‐1224‐5p exerted tumour‐suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper‐proliferation and invasion of GBM cells with MIR4435‐2HG overexpression. Clinically, the down‐regulation of miR‐1224‐5p and up‐regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435‐2HG in GBM and underlies the key function of MIR4435‐2HG‐driven GBM progression via targeting miR‐1224‐5p/TGFBR2 axis. [ABSTRACT FROM AUTHOR]

F-box protein is a substrate-receptor of SKP1-Cullin1-F-box protein (SCF) E3 ligase, but the function of many family members remains elusive. We found that F-box and WD-repeat domain-containing 2 (FBXW2) inhibits proliferation and invasion of lung cancer cells by targeting S phase kinase-associated protein 2 (SKP2) and β-catenin for degradation. Lower FBXW2 predicts a worse patient survival. Thus, FBXW2 appears a lung tumor suppressor.

The oncogenic roles of ETV4 have been revealed in multiple cancers. However, its expression and functions in lung cancer are rarely explored. Here, we firstly detected the expression of ETV4 in lung adenocarcinoma (LUAD) via online data and local experiment validation. Furthermore, we explored the functions and corresponding mechanisms of ETV4 in LUAD. Upregulation of ETV4 in LUAD is indicated by online data and our results of qPCR, Western blot and immunohistochemistry in collective tissue samples. ETV4 knockdown significantly inhibits proliferation and invasion in LUAD indicated by the outcomes of CCK8, plate clone formation, and Transwell invasion assays. Mechanistically, chromatin immunoprecipitation and luciferase reporter system assays indicated that ETV4 could directly bind at the promoter of MSI2 and promote its transcription. Furthermore, ectopic expression MSI2 can rescue the inhibitory effects caused by ETV4 knockdown in LUAD. Therefore, we proved that upregulation of ETV4 could promote proliferation and invasion of LUAD by transcriptionally upregulating MSI2 offering a potential therapy treatment target of LUAD. • ETV4 is upregulated and promotes proliferation and invasion in lung adenocarcinoma. • ETV4 regulates MSI2 transcription by directly at the promoter region. • ETV4 exerts oncogenic roles via regulating MSI2 in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to explore the expression of long non-coding RNA (lncRNA) FAM83H-AS1 and its clinical significance in ovarian cancer (OC). PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression level of lncRNA FAM83H-AS1 in 100 pairs of OC tissues and para-cancerous specimens. Meanwhile, the relationship between lncRNA FAM83H-AS1 expression and clinical features of OC patients was analyzed. According to the mean expression level of lncRNA FAM83H-AS1 (3.693), OC patients were divided into two groups, including the high-expression group (n=48) and low-expression group (n=52). After that, the association between lncRNA FAM83H-AS1 expression and clinicopathological features of OC patients was analyzed. Moreover, the correlation between the expression level of lncRNA FAM83HAS1 and the survival time of patients was estimated using the Kaplan-Meier method. After OVCAR-3 cells were transfected with Si-FAM83H-AS1 or si-NC, the expression of FAM83H-AS1 in OVCAR-3 cells was detected by qRT-PCR. RESULTS: First, qRT-PCR was used to detect the expression of lncRNA FAM83H-AS1 in OC tissues and cell lines. The results showed that lncRNA FAM83H-AS1 was significantly up-regulated in both OC tissues and OC cells when compared with normal controls. Meanwhile, lncRNA FAM83H-AS1 expression was correlated with tumor pathological grade, FIGO stage and distant metastasis of OC patients. Survival analysis was performed by the Kaplan-Meier method. The results indicated that the overall survival time of patients with higher lncRNA FAM83H-AS1 expression was markedly shorter than those with lower lncRNA FAM83H-AS1 expression. In addition, down-regulation of lncRNA FAM83H-AS1 by si-FAM83H-AS1 transfection could remarkably inhibit proliferation and invasion of OC cells in vitro. CONCLUSIONS: LncRNA FAM83H-AS1 was a novel factor involved in OC progression. Our findings suggested that FAM83H-AS1 could serve as a potential biomarker and therapeutic target for OC. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its chemoresistance and frequent late diagnosis, and suggesting that a more effective treatment approach is needed. Lysyl oxidase (LOX) is involved in important biological processes such as gene regulation, cell signaling and cell motility, its deregulation contributing to tumor formation and development. Although it is known that LOX is involved in proliferation, migration and invasion in several types of tumors, studies of LOX in ovarian cancers are scarce. To explore the molecular regulation mechanisms in ovarian cancer tumorigenesis, the expression change and the function of LOX was confirmed in ovarian tissues and cells, which suggested that LOX is a tumor suppressor gene. To further understand how LOX expression is regulated in ovarian cancer, microRNAs(miRNAs) were considered because of their role in post-transcriptional regulation of many genes. Recent work has described differential expression of mature miRNAs in human cancers. Bioinformatics prediction which was used to find the appropriate miRNA regulating LOX, revealed that miR-29b regulates LOX protein level via its binding site on the 3'UTR of LOX mRNAin ES-2 cells, a human ovarian clear cell carcinoma cell line. miR-29b knockdown inhibited proliferation and invasion in ES-2 cells. Taken together, these findings suggest that influencing LOX regulation bychanging the level of miR-29b expression could provide a novel potential approachfor treating human ovarian clear cell carcinoma.

Background: miR-4262 was identified as a tumor promoter in several cancers, but its exact role in gastric carcinoma is still largely unknown. Methods: The expression of miR-4262 was detected in gastric cancer tissues. Different concentrations of miR-4262 mimic and miR-4262 antagomir were respectively transfected into primary gastric carcinoma cells. After incubation for 72 h, the overexpression efficiencies were confirmed by qPCR, cell proliferation was detected with the CCK-8 assay, cell apoptosis was detected by using the PI/Annexin V Cell Apoptosis Kit, and cell invasion was detected with the Transwell invasion assay. The molecular mechanisms underlying the action of miR-4262 in gastric carcinoma cells were also explored. Results: In this study, we found that miR-4262 was significantly downregulated in gastric tissue from gastric cancer patients compared with that from the control group. Moreover, the level of miR-4262 was significantly lower in advanced gastric carcinoma. Additionally, lower level of miR-4262 was correlated with poorer prognosis and lower survival rate in gastric cancer patients. Then, different concentrations of miR-4262 mimic and miR-4262 antagomir were transfected into primary gastric carcinoma cells, respectively. The results showed that miR-4262 mimic suppressed proliferation and invasion and promoted cell apoptosis in a dose-dependent manner in gastric carcinoma cells. In contrast, miR-4262 antagomir increased proliferation and invasion and decreased cell apoptosis in a dose-dependent manner in gastric carcinoma cells. Furthermore, miR-4262 could directly target and suppress the expression of the proto-oncogene CD163. Conclusion: Our findings indicate that lower level of miR-4262 predicts poorer prognosis in gastric patients, and miR-4262 can target proto-oncogene CD163 to suppress gastric cancer cell proliferation and invasion. [ABSTRACT FROM AUTHOR]

Effects of polo-like kinase (PLK1) on proliferation, migration and invasion capacities of gastric cancer cells through epithelial-mesenchymal transition (EMT) were investigated. Small-interfering ribonucleic acid (siRNA) with targeted interference in PLK1 gene was designed and transfected into gastric cancer MGC-803 cells via Lipofectamine to inhibit the expression of PLK1 gene in MGC-803 cells. The proliferation of MGC-803 cells was detected via methyl thiazolyl tetrazolium (MTT) assay. The mRNA and protein expression of PLK1 and EMT-related marker (E-cadherin) was detected via real-time polymerase chain reaction and western blot analysis, respectively. The effects of interference in PLK1 gene on migration and invasion of MGC-803 cells were studied via wound healing assay and Transwell chamber assay, respectively. Results of MTT assay showed that compared with that in control group, the cell proliferation in PLK1 siRNA group was significantly inhibited (p<0.01). Compared with those in control group, the mRNA and protein expression of PLK1 in PLK1 siRNA group was significantly decreased (p<0.01), but the mRNA and protein expression of E-cadherin was obviously upregulated (p<0.01). Results of wound healing assay and invasion assay showed that the capacity of migration and invasion of MGC-803 cells in PLK1 siRNA group was significantly inhibited compared with those in control group (p<0.01). In conclusion, PLK1 enhances the proliferation, migration and invasion of gastric cancer MGC-803 cells through affecting EMT. [ABSTRACT FROM AUTHOR]

Abstract: Adipocyte fatty acid‐binding protein (FABP4) is abundant in macrophage and adipocyte. It is known to be involved in lipid metabolism. The role of FABP4 has been reported in various cancers, such as non‐small cell lung cancer, breast cancer, ovarian cancer, and prostatic cancer. However, its role remains unclear in hepatocellular carcinoma (HCC). In our study, we investigated the expression of FABP4 at both mRNA and protein levels, and by examining 175 cases of patients with cancer of the liver tissue microarray, the significance between the expression of FABP4 and clinical characteristics had been discussed. We found that FABP4 was lowly expressed in HCC tissues compared to the corresponding tissue adjacent, and the expression of FABP4 was significantly associated with the tumor size, PVTT, recurrence‐free survival and overall survival. Moreover, multivariate Cox regression analysis indicated that the expression of FABP4, Alb, AFP, HBsAg, and PVTT were independent risk factors for overall survival, and the expression of FABP4, AFP, GGT, tumor size, and encapsulation were independent risk factors for HCC recurrence. In addition, we revealed that FABP4 suppressed HCC cell proliferation and invasion in vitro. Moreover, overexpression of FABP4 led to inhibit tumor growth and decreased tumor volume in vivo. These phenotypes were associated with altered expression of Snail and p‐STAT3. Our studies thus suggest that FABP4 could be a potential target for HCC chemotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the effects of microRNA-1266 (miR-1266) on metastasis and growth in papillary thyroid carcinoma cells and to provide therapeutic targets for papillary thyroid carcinoma. PATIENTS AND METHODS: By quantitative Real-time polymerase chain reaction (PCR), miR-1266 expression level in 38 pairs of papillary thyroid carcinoma tissues and three breast cancer-derived cell lines was examined. After transfection with miR-1266 mimics, the effects of miR-1266 over-expression on cell proliferation, invasion and migration were analyzed. Further, we employed several databases for the target gene prediction. Dual-luciferase activity assay was performed to verify whether FGFR2 was the direct target gene of miR-1266. Western blotting was conducted to detect protein levels. RESULTS: MiR-1266 was significantly downregulated in papillary thyroid carcinoma tissue samples and cell lines. Over-expression of miR- 1266 in papillary thyroid carcinoma cells significantly attenuated the cell proliferation, invasion, and migration. Dual-luciferase report assay and Western blotting confirmed that FGFR2 was a target gene of miR-1266. Furthermore, up-regulation of FGFR2 partially reversed the suppressive effects of miR-1266 over-expression on cell growth and progression. CONCLUSIONS: miR-1266 could inhibit cell proliferation and progression of papillary thyroid carcinoma via targeting FGFR2. Our findings might provide a new target for the diagnosis and treatment of papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Background: High expression of collagen type X alpha 1 chain (COL10A1), a member of the collagen family, had been observed in various human cancers, but the detailed function and molecular mechanism of COL10A1 were largely unclear. Aim: The aim of this study was to investigate the expression of COL10A1 in colorectal cancer (CRC) tissues and cells and to reveal its biological function and mechanism in CRC. Materials and methods: Immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (QPCR) and Western blot experiments were used to determine the clinical relevance between expression levels of COL10A1 and CRC. Results: Compared with normal tissues, COL10A1 expression was significantly higher in CRC tissues. Biological functional experiments showed that overexpression of COL10A1 enhanced proliferation, migration, and invasion of CRC cells, and knockdown of COL10A1 inhibited tumorigenesis in vivo. Western blot assays showed that COL10A1 promoted the process of epithelial-mesenchymal transition (EMT). The overexpression of COL10A1 was associated with adverse prognosis in CRC by tissue microarray (TMA) analysis. Conclusion: Our findings had provided evidences to support the fact that COL10A1 was abnormally up-expressed in CRC and involved in the progression of CRC and the process of EMT. Furthermore, we demonstrated that the high-level expression of COL10A1 was an independent risk factor of prognosis and overall survival in CRC patients. These suggested that COL10A1 might be a new potential target for cancer therapy in the future. [ABSTRACT FROM AUTHOR]

Aims: Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell (HuPCaSC) proliferation and invasion. Materials and Methods: We used methyl thiazolyl tetrazolium and Transwell assays to examine the proliferation and invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1- DIO3 imprinted genomic region in the cells and in tumor tissues from patients with PCa were examined using microarray and quantitative PCR. Results: The median inhibitory concentration of curcumin for HuPCa cells significantly inhibited HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247 expression levels in the DLK1- DIO3 imprinted gene cluster were significantly different between the curcumin-treated and control HuPCaSCs. Overexpression of these positive miRNAs significantly increased the inhibition rates of miR-770-5p- and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247 expression levels than high-grade tumor tissues. Conclusions: Curcumin can suppress HuPCaSC proliferation and invasion in vitro by modulating specific miRNAs in the DLK1- DIO3 imprinted gene cluster. [ABSTRACT FROM AUTHOR]

miR-101-3p has been identified as a tumor suppressor in several cancers, but its exact role in gastric adenocarcinoma is still largely unknown. In this study, we found that, compared with the RGM-1 human normal gastric epithelial cells, miR-101-3p was significantly downregulated in all six human gastric adenocarcinoma cell lines, including BGC-823, MNK-45, MGC-803, SGC-7901, AGS, and HGC-27. Overexpression of miR-101-3p suppressed both the proliferation and invasion of AGS gastric adenocarcinoma cells, and knockdown of miR-101-3p displayed the opposite effect. In addition, miR-101-3p could directly target and suppress the expression of the serum response factor (SRF) gene, which is a transcription factor of HOTAIR, a well-characterized tumor promoter lncRNA. miR-101-3p negatively regulated SRF-mediated transcription of HOTAIR. Moreover, silencing of either SRF or HOTAIR could counteract the promotion of gastric adenocarcinoma cell proliferation and invasion by miR-101-3p inhibition. Our findings indicate that miR-101-3p suppresses HOTAIR-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To dissect the functioning mode of miR-30c on giant cell tumor of bone cell metastasis and growth and provide therapeutic targets for giant cell tumor of bone. PATIENTS AND METHODS: By quantitative Real-time polymerase chain reaction (qRT-PCR), miR-30c expression level in 62 pairs of giant cell tumor of bone cells tissue samples and five breast cancer-derived cell lines. Using miR-30c mimics and inhibitors, we analyzed the effects of miR-30c over-expression and knockdown on cell proliferation, invasion, and migration. Dual-luciferase activity assay was recruited to examine the potential target gene HOXA1, which predicted by several databases. Protein level was studied using Western blot. RESULTS: MiR-30c expressed significantly lower in giant cell tumor of bone tissue samples and cell lines. Over-expression miR-30c in giant cell tumor of bone cells decreased the cell proliferation, invasion, and migration abilities while down-regulation miR-30c in giant cell tumor of bone cells increased these abilities oppositely. Dual-luciferase and Western blot confirmed HOXA1 as a target gene of miR-30c. Furthermore, up-regulation of HOXA1 reserved the suppressive effect of miR-30c over-expression on cell growth and progression. CONCLUSIONS: miR-30c could suppress giant cell tumor of bone cell proliferation and progression via HOXA1, which might provide a new target for giant cell tumor of bone diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Many studies have demonstrated that curcumin can effectively inhibit the proliferation, invasion, and tumorigenesis of prostate cancer cells in vitro and in vivo. In this study, CD44 + /CD133 + human prostate cancer stem cells (HuPCaSCs) were isolated from the prostate cancer cell lines Du145 and 22RV1. Curcumin treatment of these cells resulted in the inhibition of in vitro proliferation and invasion, and cell cycle arrest. The expression levels of cell cycle proteins (Ccnd1 and Cdk4) and stem cell markers (Oct4, CD44, and CD133) were decreased in curcumin-treated HuPCaSCs. Microarray analysis and northern blotting assays indicated that miR-145 was overexpressed in curcumin-treated HuPCaSCs. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, bioinformatics analysis and luciferase activity assays showed that the lncRNA-ROR and Oct4 mRNA both contain miR-145 binding sites, and Oct4 and lncRNA-ROR directly compete for microRNA binding. Curcumin induced high miR-145 expression and inhibited the expression of lncRNA-ROR. The tumorigenicity of curcumin- treated HuPCaSCs in nude mice was significantly reduced. In summary, reducing the expression of endogenous lncRNA-ROR could effectively increase the available concentration of miR-145 in HuPCaSCs, where miR-145 prevents cell proliferation by decreasing Oct4 expression. In particular, we hypothesized that lncRNA-ROR may act as a ceRNA, effectively becoming a sink for miR-145, thereby activating the derepression of core transcription factors Oct4. Thus, curcumin suppresses the proliferation, in vitro invasion, and tumorigenicity of HuPCaSCs through ceRNA effect of miR-145 and lncRNA-ROR caused. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is the leading cause of cancer-related death among all the gynecological malignancies of the female genital system, and its incidence and mortality rates continue to rise. B-cell translocation gene 3 (BTG3) plays an important role in the occurrence and development of numerous cancers. However, the role of BTG3 in EOC remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of BTG3 in EOC. We found that BTG3 protein expression was significantly lower in human EOC cell lines. Next, BTG3 upregulation by transfection with pcDNA3.1-BTG inhibited cell proliferation and invasion but promoted cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. In addition, BTG3 knockdown by small interfering RNA promoted cell proliferation and invasion, but inhibited cell apoptosis in 2 human EOC cell lines, SKOV-3 and HO-8910 cells. Importantly, several proteins, including phosphorylation serine/threonine kinase (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β), and β-catenin, were markedly decreased by BTG3 upregulation, whereas increased by BTG3 knockdown. Taken together, the results of our study suggest that BTG3 overexpression could inhibit cell proliferation and invasion and promotes cell apoptosis in EOC cell, possibly by regulating the AKT/GSK3β/β-catenin signaling pathway, providing novel insights into the treatment of EOC through BTG3 overexpression. [ABSTRACT FROM AUTHOR]

Background: Isoflurane is one of the most common general anaesthetics used during surgical procedures, including tumour resection. However, the effects of isoflurane on the viability and migration capacity of cancer cells, specifically in the context of brain cancer cells, remain unclear. Therefore, the aim of this study was to evaluate the influence that isoflurane has on the function of glioblastoma stem cells (GCSs) in regards to cell proliferation, survival and migration.Method: U251-GSCs were exposed to isoflurane at clinically relevant concentrations and incubation times. The effects on proliferation, survival and migration capacities of the cells were evaluated in vitro. The potential risk was assessed in mice by intracranial injection of U251-GSCs pretreated with isoflurane. Furthermore, the average tumour volume and migration distance of U251-GSCs from the tumour centre were calculated.Results: Exposure of U251-GSCs to 1.2% isoflurane for 6 h resulted in increased proliferation (P<0.05) and decreased apoptosis rate (P<0.05) when compared with the control group. In addition, isoflurane exposure caused increased migration capacity in vitro (P<0.05) and the distance migrated was increased in vivo (P<0.05).Conclusion: Clinically relevant concentrations and incubation times of isoflurane could promote the viability and mobility of U251-GSCs, suggesting this general anaesthetic may have detrimental effects in glioblastoma by facilitating its growth and migration. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNA (lncRNA) ATB belongs to an active modulator in multiple cancers, but its expression along with potential underlying non-small cell lung cancer (NSCLC) is obscure. Our study aimed to investigate the role and potential mechanism of LncRNA ATB in NSCLC., Methods: LncRNA ATB expression in NSCLC tissues and cell lines was detected by qRT-PCR. Effects of LncRNA ATB on NSCLC cell proliferation, migration and invasion were assessed by MTS, colony formation and transwell assays. The connection among LncRNA ATB, miR-200b and fibronectin 1 (FN1) was determined by bioformatics prediction and luciferase reporter assay., Results: In this research, upregulation of LncRNA ATB was discovered in NSCLC tissue samples and cell lines. LncRNA ATB was positively related to advanced tumor phase as well as lymph node metastasis. Cell function assays reflected LncRNA ATB expedited NSCLC cells proliferation, migration and invasion. LncRNA ATB promoted fibronectin 1 (FN1) expression via inhibiting miR-200b. Furthermore, LncRNA ATB depletion suppressed NSCLC cells proliferation, migration and invasion, while miR-200b inhibitor or pcDNA-FN1 rescued these effects., Conclusion: In summary, our outcomes elucidated that LncRNA ATB/miR-200b axis expedited NSCLC cells proliferation, migration and invasion by up-regulating FN1., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Objective To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy. Methods The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real-time PCR and western blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy. Results The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased ( P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 ± 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of β-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E-cadherin decreased, while the one of vimentin increased. Conclusions siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its chemoresistance and frequent late diagnosis, and suggesting that a more effective treatment approach is needed. Lysyl oxidase (LOX) is involved in important biological processes such as gene regulation, cell signaling and cell motility, its deregulation contributing to tumor formation and development. Although it is known that LOX is involved in proliferation, migration and invasion in several types of tumors, studies of LOX in ovarian cancers are scarce. To explore the molecular regulation mechanisms in ovarian cancer tumorigenesis, the expression change and the function of LOX was confirmed in ovarian tissues and cells, which suggested that LOX is a tumor suppressor gene. To further understand how LOX expression is regulated in ovarian cancer, microRNAs (miRNAs) were considered because of their role in post-transcriptional regulation of many genes. Recent work has described differential expression of mature miRNAs in human cancers. Bioinformatics prediction which was used to find the appropriate miRNA regulating LOX, revealed that miR-29b regulates LOX protein level via its binding site on the 3'UTR of LOX mRNA in ES-2 cells, a human ovarian clear cell carcinoma cell line. miR-29b knockdown inhibited proliferation and invasion in ES-2 cells. Taken together, these findings suggest that influencing LOX regulation by changing the level of miR-29b expression could provide a novel potential approach for treating human ovarian clear cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) are emerging as key regulators governing fundamental biological processes, and their disorder expression involves in tumorigenesis. SPRY4-IT1 (SPRY4 intronic transcript 1), a lncRNA derived from an intron within SPRY4 gene, involves in multiple cancers development. However, the expression pattern and biological function of SPRY4-IT1 in gastric cancer is still not well documented. Hence, we carried out the present study to investigate the potential role of SPRY4-IT1 in gastric carcinogenesis. Methods: QRT-PCR was performed to detect the expression of SPRY4-IT1 in 61 pairs of gastric cancer samples. Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of SPRY4- IT1. The effect of SPRY4-IT1 on proliferation was evaluated by MTT and colony formation assays. Gastric cancer cells transfected with pCDNA-SPRY4-IT1 were injected into nude mice to study the effect of SPRY4-IT1 on tumorigenesis and metastasis in vivo. Protein levels of SPRY4-IT1 targets were determined by western blot or fluorescence immunohistochemistry. ChIP assays were performed to investigate the effect of DNMT1 on SPRY4-IT1 expression. Differences between groups were tested for significance using Student's t test (two-tailed). Results: SPRY4-IT1 expression is decreased in gastric cancer tissues and associated with larger tumor size, advanced pathological stage, deeper depth of invasion and lymphatic metastasis. Patients with lower SPRY4-IT1 expression had a relatively poor prognosis. DNA methylation may be a key factor in controlling the SPRY4-IT1 expression. Furthermore, SPRY4-IT1 contributed to gastric cancer cells metastasis might partly via regulating epithelial-mesenchymal transition (EMT) process. Conclusion: Low expression of SPRY4-IT1 is involved in progression and metastasis of gastric cancer and may represent a novel biomarker of poor prognosis in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common types of cancer and is the leading cause of cancer-related mortality worldwide. Estrogens are known to be involved in the development and progression of non-small-cell lung cancer (NSCLC). These effects are initially mediated through binding of estrogen to estrogen receptors (ERs), in particular ERβ2. Our preliminary studies demonstrated that ERβ2 and interleukin-12 receptorβ2 (IL-12Rβ2) expression are correlated in NSCLC. The present study investigated the expression of these proteins in NSCLC cells and how changes in their expression affected cell proliferation and invasion. In addition, it aimed to explore whether p38 mitogen-activated protein kinase (p38MAPK) is involved in the regulation of IL-12Rβ2 expression by ERβ2. An immunocytochemical array was used to observe the distribution of ERβ2 and IL-12Rβ2. Co-immuoprecipitation was employed to observe the interaction between p38MAPK and IL-12Rβ2, by varying the expression of ERβ2 and p38MAPK. Western-blot analysis and reverse transcription-polymerase chain reaction assays were used to investigate the mechanism underlying ERβ2 regulation of IL-12Rβ2 expression. 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, scratch wound healing and Transwell assays were used to investigate the impact of ERβ2 on proliferative, invasive and migratory abilities of NSCLC cells. ERβ2 was predominantly found in the cytoplasm and nucleus, whilst IL-12Rβ2 was largely confined to the cytoplasm, although a degree of expression was observed in the nucleus. Compared with normal bronchial epithelial cells, IL-12Rβ2 and ERβ2 were overexpressed in the NSCLC cell groups. Coimmuoprecipitation demonstrated an interaction between p38MAPK and IL-12Rβ2. ERβ2 appeared to upregulate IL-12Rβ2 expression and inhibition of p38MAPK attenuated this effect. ERβ2 and IL-12Rβ2 expression inhibited the proliferation, metastasis and invasion of NSCLC cell lines, but knockout of IL-12Rβ2, even in the presence of ERβ2, led to an increase in NSCLC cell proliferation and invasiveness. In conclusion, to the best of our knowledge this study is the first to demonstrate that IL-12Rβ2 may be important in the mechanisms underlying ERβ2 inhibition of NSCLC development, and that this interaction may be mediated via p38MAPK. [ABSTRACT FROM AUTHOR]

Abstract: TFF1 is a small, secreted protein in the TFF family that has a pivotal role as a motogenic factor in epithelial restitution and cell motility, and as a tumor suppressor gene in the stomach. In this study, we identified TFF1 as a novel target gene of miRNA-423-5p. miRNA-423-5p negatively regulated the expression of TFF1 by binding to its 3′UTR and participated in proliferation/invasion-related processes via a TFF1-dependent manner in gastric cancer cells. Our findings suggested that miR-423-5p may be a novel target for the future development of specific therapeutic interventions for gastric cancer. [Copyright &y& Elsevier]

Background Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. Methods HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. Results HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. Conclusions HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNAdirected diagnostics and therapeutics against this disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cyclosporin A (CsA) is a powerful immunosuppressive that has been widely used to prevent organ rejection and to treat certain autoimmune diseases. Our previous study showed that CsA at low concentrations could promote proliferation and invasion, and inhibit apoptosis, of human first trimester trophoblasts. In the present study, we further explored the potential mechanism and signal pathway. [ABSTRACT FROM PUBLISHER]

Ovarian cancer (OC) has the highest mortality rate among gynecological cancers, which progresses owing to dysregulated microRNAs (miRNAs) expression. Our study attempts to reveal the mechanism by which decreased miR-324-3p expression suppresses OC proliferation. Quantitative real-time PCR, western blotting, in situ hybridization, and immunohistochemistry were performed to estimate miR-324-3p and WNK2 expression levels in OC cells and tissues. Cell Counting Kit-8, colony formation, EdU, and transwell assays were performed to analyze the influence of miR-324-3p and WNK2 on the proliferation and invasion ability of OC cells. Subsequently, xenograft models were established to examine the effects of WNK2 on OC cell proliferation in vivo, and databases and luciferase reporter assays were used to test the relationship between miR-324-3p and WNK2 expression. Then, we showed that miR-324-3p expression is decreased in OC cells and tissues, indicating its inhibitory effect on OC cell proliferation. Quantitative real-time PCR and luciferase reporter assays demonstrated that miR-324-3p inhibited WNK2 expression by directly binding to its 3' untranslated region. WNK2, an upregulated kinase, promotes the proliferation and invasion of OC cells by activating the RAS pathway. Moreover, WNK2 can partly reverse the inhibitory effects of miR-324-3p on OC cell proliferation. Hence, we demonstrate that miR-324-3p suppressed ovarian cancer progression by targeting the WNK2 /RAS pathway. Our study provides theoretical evidence for the clinical application potential of miR-324-3p.

SH3 domain-containing kinase-binding protein 1 (CIN85), an 85 kDa protein known to be a member of the signal adaptor family, is abnormally expressed in several human malignancies and has been found to be involved in the growth, migration and invasion of these tumors. The objective of the present study was to clarify the clinical significance of CIN85 in human esophageal squamous cell carcinoma (ESCC), as well as its in vitro functions. CIN85 expression was evaluated in 129 cases of ESCC and its adjacent normal tissues using immunohistochemistry to explore its clinical relevance and prognostic value. The functions of CIN85 in the ESCC TE1 cell line were analyzed in vitro using the interfering short hairpin RNA silencing technique. MTS, wound healing, clone formation and Transwell assays were used to detect the proliferation, migration and invasion of ESCC cells. CIN85 expression was identified mainly in ESCCs and their adjacent normal tissues, and the high expression of CIN85 was significantly associated with advanced Tumor Node Metastasis stage and lymph node metastasis. CIN85 gene silencing significantly inhibited TE1 cell proliferation, migration and invasion. These results demonstrated that CIN85 was highly expressed in advanced stage ESCC and lymph node metastasis, and played a critical role in tumor proliferation and progression. Therefore, CIN85 may be a promising therapeutic target for human ESCC. [ABSTRACT FROM AUTHOR]

Tomoregulin-2 (TMEFF2) is a single-pass transmembrane protein whose specific functions and mechanisms in endometrial carcinoma (EC) remain unclear. The aim of this study was to investigate the expression, prognostic role, and potential regulatory mechanisms of TMEFF2 in EC. The expression and prognosis of TMEFF2 in EC were analyzed via bioinformatics and verified by immunohistochemistry and survival analysis. Proliferation, invasion, and migration of EC cells in vitro were assessed by cell functional assays, while epithelial–mesenchymal transition (EMT) markers and key signaling pathway proteins were evaluated by western blotting. The expression of TMEFF2 in EC was significantly higher than that in atypical hyperplasia and normal endometrium, the high expression of TMEFF2 was correlated with advanced stage, poor differentiation, and lymph node metastasis, and also predicted a poor prognosis of EC. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that TMEFF2 and its related genes were enriched in the central nervous system, cell adhesion, signal transduction, and several critical signaling pathways. We also elucidated TMEFF2 networks of kinase, microRNA, and transcription factor targets. In vitro , the proliferation, invasion, and migration abilities of EC cells decreased after TMEFF2 downregulation. Downregulation of TMEFF2 reduced the activation of MAPK and PI3K signaling pathways, and inhibited EMT. TMEFF2 plays an important role in the initiation, development, and malignant behavior of EC and can be a potential target for early diagnosis and treatment in EC. [ABSTRACT FROM AUTHOR]

Accumulating evidence has indicated that microRNAs can regulate downstream signaling pathways and play an important role in various tumors. In this study, we found that miR-223-3p was differentially expressed in 40 paired gastric cancer tissues and adjacent tissues and that miR-223-3p was positively correlated with tumor invasion depth and lymph node metastasis. Luciferase reporter assay confirmed that Arid1a was the target gene of miR-223-3p. Functional assays showed that miR-223-3p promoted the proliferation and invasion of gastric cancer cells by regulating the expression of Arid1a. We also confirmed that miR-223-3p regulated the growth of gastric cancer cells in vivo, while an antagomir against miR-223-3p significantly inhibited tumor growth. In conclusion, our results demonstrated that miR-223-3p inhibits gastric cancer cell progression by decreasing the expression of Arid1a. Therefore, miR-223-3p may act as a potential therapeutic target for patients with gastric cancer., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

F-box protein is a substrate-receptor of SKP1-Cullin1-F-box protein (SCF) E3 ligase, but the function of many family members remains elusive. We found that F-box and WD-repeat domain-containing 2 (FBXW2) inhibits proliferation and invasion of lung cancer cells by targeting S phase kinase-associated protein 2 (SKP2) and β-catenin for degradation. Lower FBXW2 predicts a worse patient survival. Thus, FBXW2 appears a lung tumor suppressor. [ABSTRACT FROM AUTHOR]

Accumulating evidence has highlighted the critical role of cullin 4B (CUL4B) in driving tumourigenesis in several malignancies, including gastric cancer (GC); however, the mechanisms underlying CUL4B upregulation remain unclear. The dysregulation of microRNAs (miRNAs or miRs) is known to be involved in tumourigenesis. In this study, we report that the expression of miR‑381 and miR‑489 is downregulated and is negatively correlated with that of CUL4B in GC tissues and cell lines. Further analysis verified that miR‑381 and miR‑489 directly targeted CUL4B. CUL4B silencing inhibited cell proliferation, migration and invasion by inactivating the Wnt/β‑catenin pathway. miR‑381/miR‑489 overexpression recapitulated the effects of CUL4B silencing, while CUL4B restoration negated the suppressive effects induced by the ectopic expression of miR‑381/miR‑489. Furthermore, miR‑381/miR‑489 exerted tumour suppressive functions by inactivating the Wnt/β‑catenin pathway through the targeting of CUL4B. Taken together, the findings of this study suggest that the miR‑381/miR‑489‑mediated expression of CUL4B modulates the proliferation and invasion of GC cells via the Wnt/β‑catenin pathway, which indicates that the miR‑381/miR‑489‑CUL4B axis is critical in the control of GC tumourigenesis.

Mounting evidence shows that the long non-coding RNA MALAT1 plays a pivotal role in tumorigenesis and metastasis, but the functional significance of MALAT1 in bladder transitional cell carcinoma (BTCC) remains unclear. MALAT1 expression was measured in 56 BTCC patients and 2 BTCC cell lines by real-time PCR. The effects of MALAT1 on BTCC cells were investigated by over-expression approaches in vitro and in vivo . Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were validated through bioinformatic analysis and luciferase assay. MALAT1 up-regulation positively correlated with advanced clinical pathological stage and shorter survival of BTCC patients. Furthermore, MALAT1 over-expression promoted proliferation, migration and invasion of BTCC cells in vitro and in vivo . Particularly, MALAT1 may function as a ceRNA to sponge miR-124, thus modulating the derepression of foxq1, miR-124 target gene, in post-transcriptional levels. The positive MALAT1/foxq1 interaction was confirmed by bivariate correlation analysis, and this positive correlation was of great significance in BTCC tumor growth and metastasis, also accompanied by EMT changes. Overall, this ceRNA regulatory network concerning MALAT1 and the positive MALAT1/foxq1 correlation benefit a better understanding of BTCC pathogenesis and promote the feasibility of lncRNA-directed therapy against this disease., Competing Interests: None.

Lasp1 (LIM and SH3 domain protein 1) promotes tumor proliferation and invasion in multiple cancer entities including non-small cell lung cancer (NSCLC). However, the molecular mechanism is uncertain to date. In the present study, using immunohistochemistry, we found that Lasp1 expression was significantly correlated with tumor size ( P =0.005), advanced TNM stage ( P =0.042), positive regional lymph node metastasis ( P =0.034) and poor overall survival ( P <0.001). Similar results were seen in patients with squamous cell lung carcinoma ( P =0.003 for larger tumor size, P =0.017 for advanced TNM stage, P =0.003 for positive lymph node metastasis and P <0.001 for poor overall survival) but not in patients with lung adenocarcinoma ( P >0.05). Proliferation and invasion assay showed that Lasp1 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent western blot results revealed that Lasp1 promoted the expression of Cyclin A2, CyclinB1, and Snail, and inhibited the expression of E-cadherin. Lasp1 directly interacted with FAK and facilitated the expression of phosphorylated FAK (Tyr397) and AKT (Ser473). Incorporation of both FAK inhibitor and AKT inhibitor counteracted the upregulating expression of Cyclin A2, CyclinB1, and Snail, and downregulating expression of E-cadherin expression induced by Lasp1 overexpression. Interestingly, inhibition of FAK signaling pathway attenuated the phosphorylation of AKT, but inhibition of AKT signaling pathway did not affect the phosphorylation of FAK. In conclusion, Lasp1 facilitated tumor proliferation and invasion of NSCLC through directly binding to FAK and enhancing the phosphorylation of FAK (Tyr397) and AKT (Ser473). Lasp1 may be a novel therapeutic target in the treatment of NSCLC patients., Competing Interests: CONFLICTS OF INTEREST The authors disclosed no potential conflicts of interest.

Background: Cancer-associated fibroblasts (CAFs) are dominant components of the prostate cancer (PCa) stroma. However, the contrasting effects of CAFs and adjacent normal prostate fibroblasts (NPFs) are still poorly defined. The senescence of non-immortalized CAFs after subculture may limit the cell number and influence experimental results of in vitro studies. In this study, we immortalized CAFs to study their role in PCa carcinogenesis, proliferation, and invasion., Materials and Methods: We cultured and immortalized CAFs and NPFs, then compared their effect on epithelial malignant transformation by using in vitro co-culture, soft agar assay, and a mouse renal capsule xenograft model. We also compared their roles in PCa progression by using in vitro co-culture, cell viability assays, invasion assays, and a mouse xenograft model. For the mechanistic study, we screened a series of growth factors by using real-time polymerase chain reaction., Results: The CAFs and NPFs were successfully cultured, immortalized, and characterized. The CAFs were able to transform prostate epithelial cells into malignant cells, but NPFs were not. The CAFs were more active in promoting proliferation of and invasion by PCa cells, and in secreting higher levels of a series of growth factors., Conclusion: The immortalized CAFs were more supportive of PCa carcinogenesis and progression. Targeting CAFs might be a potential option for PCa therapy. Immortalized CAFs and NPFs will also be valuable resources for future experimental exploration., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Recent studies have shown that increased syndecan-1 (SDC1) expression in human glioma is associated with higher tumor grades and poor prognoses, but its oncogenic functions and the underlying molecular mechanisms remain unknown. Here, we examined SDC1 expression in datasets from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus. Elevated SDC1 expression in glioma was closely associated with increases in tumor progression and shorter survival. We also examined SDC1 expression and evaluated the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown attenuated proliferation and invasion by glioma cells and markedly decreased PCNA and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased phosphorylation of the c-src/FAK complex and its downstream signaling molecules, Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic target in the treatment of glioma.

ST6Gal-I sialyltransferase adds α2,6-linked sialic acids to the terminal ends of glycan chains of glycoproteins and glycolipids. ST6Gal-I is reportedly upregulated in many cancers, including hepatocellular carcinoma, ovarian cancer and breast cancer. However, the expression and function of ST6Gal-I in prostate cancer (PCa) and the mechanism underlying this function remain largely unknown. In this study, we observed that ST6Gal-I expression was upregulated in human PCa tissues compared to non-malignant prostate tissues. High ST6Gal-I expression was positively correlated with Gleason scores, seminal vesicle involvement and poor survival in patients with PCa. ST6Gal-I knockdown in aggressive prostate cancer PC-3 and DU145 cells significantly inhibited the proliferation, growth, migration and invasion capabilities of these cells. ST6Gal-I knockdown decreased the levels of several PI3K/Akt/GSK-3β/ β-catenin pathway components, such as p-PI3K, (Ser473)p-Akt, (Ser9)p-GSK-3β and β-catenin. Furthermore, targeting this pathway with a PI3K inhibitor or Akt RNA interference decreased p-Akt, p-GSK-3β and β-catenin expression, resulting in decreased PC-3 and DU145 proliferation, migration and invasion. Taken together, these results indicate that ST6Gal-I plays a critical role in cell proliferation and invasion via the PI3K/Akt/GSK-3β/β-catenin signaling pathway during PCa progression and that it might be a promising target for PCa prognosis determination and therapy.

MicroRNAs (miRNAs) have emerged as critical modulators of carcinogenesis and tumor progression. In the present work, we sought to identify the biological function of miR-155 as well as its underlying mechanism in clear cell renal cell carcinoma (ccRCC). We examined the expression of miR-155 in clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-155 both in vitro and in vivo. The results of this analysis indicated that miR-155 activity was significantly upregulated in ccRCC tissues compared with the corresponding normal tissues. miR-155 was associated with ccRCC aggressiveness in both cell lines and clinical specimens, and a specific and inverse correlation between miR-155 and E2F2 expression was found in human ccRCC samples. Overexpression of miR-155 in 786-O cells decreased E2F2 expression while reduction of miR-155 by anti-miR-155 in ACHN cells elevated E2F2 expression. Re-expression of E2F2 in 786-O cells repressed the cell migration/invasion abilities elevated by miR-155, whereas knockdown of E2F2 in ACHN cells restored these cellular functions hampered by the miR-155 inhibitor. Using Western blot and luciferase reporter assays, we determined that E2F2 was a direct target of miR-155. Taken together, the in vitro and in vivo results demonstrate that miR-155 functions as a tumor-promoting miRNA by targeting E2F2 in ccRCC.

ZNF217 is an alternatively spliced Kruppel-like transcription factor that has recently been implicated to play a role in human carcinogenesis. Here, we used immunohistochemistry (IHC) to show that ZNF217 protein is overexpressed in nearly 60% of ovarian tumor samples. The disease-free survival time was shorter in patients with positive ZNF217 expression than in ZNF217-negative patients (P=0.042). Fluorescence in situ hybridization (FISH) analysis showed ZNF217 genomic amplification in the poorly differentiated tumors, suggesting that ZNF217 is associated with the progression of ovarian cancer. Invasion was enhanced in HO-8910 cells stably transfected with constructs carrying full-length ZNF217 relative to cells transfected with the empty vector. To confirm our findings in vivo, we performed a tumorigenicity assay in nude mice inoculated with the HO-8910 overexpressing ZNF217 cells. As expected, tumors grown in the ZNF217 group were more invasive and prone to metastasis than those formed control groups. Based on these clinical and laboratory observations, we conclude that ZNF217 may contribute to ovarian cancer invasion and metastasis, and associated with worse clinical outcomes.