miR-101 regulates expression of EZH2 and contributes to progression of and cisplatin resistance in epithelial ovarian cancer.

In order to determine the expression pattern of miR-101 in epithelial ovarian neoplasms and assess the functions and mechanism of miR-101 in tumorigenesis, we detected the expression of miR-101 and zeste homolog 2 (EZH2) in normal, benign, and malignant ovarian tissues and used miR-101 lentivirus infection to increase miR-101 expression in ovarian cancer cells and drug-resistant cancer cells. We found that miR-101 was underexpressed in epithelial ovarian cancer tissues, which significantly correlated with poor cell differentiation, advanced International Federation of Gynecology and Obstetrics (FIGO) stages, and ovarian cancer cell cisplatin resistance. miR-101 overexpression decreased the expression of EZH2, reduced proliferation and migration of ovarian cancer cells, and resensitized drug-resistant cancer cells to cisplatin-induced cytotoxicity, suggesting the important role miR-101 plays in ovarian cancer that may be associated with its function as a regulator targeting EZH2. Our findings show the potential of miR-101 as a diagnostic marker and new therapeutic target for patients with epithelial ovarian cancer.

DSG2 and c-MYC Interact to Regulate the Expression of ADAM17 and Promote the Development of Cervical Cancer.

Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism. Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression. Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05). Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.

Upregulation of lncRNA GATA6-AS suppresses the migration and invasion of cervical squamous cell carcinoma by downregulating MTK-1.

The diagnosis and treatment of cervical squamous cell carcinoma is challenged by difficulties in the determination of tumor invasion. GATA binding protein 6 antisense (GATA6-AS) is a recently identified long non-coding RNA that exhibits critical functions in the growth of endothelial cells; however, to the best of our knowledge, its involvement in other physiological and pathological processes is unknown. By reverse transcription-quantitative polymerase chain reaction, the present study examined the expression of GATA6-AS in tumor tissues and adjacent healthy tissues, and the serum from patients with cervical squamous cell carcinoma and healthy controls. The diagnostic and prognostic potentials of GATA6-AS for cervical squamous cell carcinoma were analyzed by receiver operating characteristic curve analysis and survival curve analysis, respectively. Associations between the serum levels of GATA6-AS and clinical characteristics of patients with cervical squamous cell carcinoma were analyzed by a χ2 test. A GATA6-AS overexpression vector was transfected into cervical squamous cell carcinoma cells, and the effects on cell migration and invasion were investigated by Transwell migration and invasion assays, respectively. The expression of mitogen-activated protein kinase kinase 4 (MTK-1) following transfection with the GATA6-AS overexpression vector was detected by western blot analysis. It was identified that the expression levels of GATA6-AS were lower in tumor tissues compared with healthy tissues. In addition, serum levels of GATA6-AS were higher in patients compared with healthy controls. The serum levels of GATA6-AS were associated with tumor metastasis, and may serve as a potential diagnostic and prognostic marker for cervical squamous cell carcinoma. Furthermore, GATA6-AS overexpression inhibited cancer cell migration and invasion. The expression levels of MTK-1 were also reduced following GATA6-AS overexpression. Therefore, the present study proposed that downregulated GATA6-AS expression was associated with tumor metastasis in cervical squamous cell carcinoma, and that GATA6-AS expression may inhibit cancer cell migration and invasion by downregulating MTK-1.

Cancer-associated fibroblasts enhance the migration ability of ovarian cancer cells by increasing EZH2 expression.

The tumor microenvironment is thought to affect malignant transformation and tumor progression. The histone methyltransferase, enhancer of zeste homologue 2 (EZH2), has recently been suggested to play a critical role in the tumorigenesis of several types of human cancer. The aim of this study was to investigate the effects of cancer-associated fibroblasts (CAFs) on the expression of EZH2 and the migration ability of ovarian cancer cells, in order to explore the link between the tumor microenvironment and epigenetic regulation. The ovarian cancer cell lines, A2780, SKOV3 and ES2, were indirectly co-cultured with primary ovarian CAFs or normal fibroblasts (NFs). The migration ability of the ovarian cancer cells was determined by Transwell migration assay. The expression levels of EZH2 were assessed by quantitative reverse transcription PCR (qRT-PCR) and western blot analysis. The A2780-shEZH2 cells (A2780 cells transfected with shRNA targeting EZH2) were indirectly co-cultured with CAFs or NFs, and the changes in the expression levels of EZH2 and the migration ability of the cells were detected. The migration ability of the A2780, SKOV3 and ES2 cells co-cultured with CAFs was significantly enhanced (P<0.05) compared with the NF group and the cells cultured alone. The expression of EZH2 in the A2780, SKOV3 and ES2 cells was significantly increased following co-culture with CAFs (P<0.001) compared with the cells cultured alone but not those cultured with NFs. The migration ability of the A2780-shEZH2 cells was not significantly increased following co-culture with CAFs (P>0.05). Our data indicate that CAFs enhance the migration ability of ovarian cancer cells partly by increasing EZH2 expression.