Bing Li

MiR-590-5p promotes cisplatin resistance via targeting hMSH2 in ovarian cancer

The mechanisms of ovarian cancer generate chemotherapy resistance are still unclear. This study aimed to explore the role of microRNA (miR)-590-5p in regulating hMSH2 expression and cisplatin resistance in ovarian cancer. MiR-590-5p was identified as a regulator of hMSH2 with miRDB database and Target Scan database. Then cisplatin sensitive cell line (SKOV3) and resistant cell line (SKOV3-DDP) of ovarian cancer were cultured for cell functional assay and molecular biology assay. The expression levels of MiR-590-5p and hMSH2 were compared between the two cell lines. Dual luciferase reporter assay was used to verify the targeted regulatory relationship between miR-590-5p and hMSH2. CCK-8 assay and cell apoptosis assay were utilized to assess the role of MiR-590-5p and hMSH2 in cell viability under cisplatin. The expression of hMSH2 was significantly decreased, and miR-590-5p was significantly up-regulated in SKOV3-DDP. Up-regulation of hMSH2 weakened the viability of SKOV3 and SKOV3-DDP cell under cisplatin. Transfection with miR‑590-5p mimics reduced the expression of hMSH2 and enhanced the viability of ovarian cancer cells under cisplatin, whereas inhibition of miR‑590-5p increased the expression of hMSH2, and decreased ovarian cancer cells' viability under cisplatin. Furthermore, luciferase reporter assay showed that hMSH2 was a direct target of miR-590-5p. The present study demonstrates that miR‑590-5p promotes cisplatin resistance of ovarian cancer via negatively regulating hMSH2 expression. Inhibition of miR‑590-5p decreases ovarian cancer cells' viability under cisplatin. Thus miR‑590-5p and hMSH2 may serve as therapeutic targets for cisplatin resistant ovarian cancer.

RETRACTED ARTICLE: Repression of lncRNA PART1 attenuates ovarian cancer cell viability, migration and invasion through the miR-503-5p/FOXK1 axis

Abstract Background Ovarian cancer (OC) is a female malignant tumor with a high fatality rate. Long non-coding RNAs (lncRNAs) are deeply involved in OC progression. The aim of this study is to explore the specific mechanism of lncRNA prostate androgen-regulated transcript 1 (PART1) in OC. Methods Quantitative real time PCR was utilized to determine the expression levels of PART1, microRNA (miR)-503-5p and forkhead-box k1 (FOXK1) in OC tissues and/or cells. The cell viability, migration, and invasion in OC were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, wound healing assay and transwell invasion assay, respectively. Flow cytometry was used to analyze the cell apoptosis. The xenograft tumor was conducted in nude mice to verify the effect of PART1 knockdown on OC in vivo. The target relationships among PART1, miR-503-5p and FOXK1 were predicted by StarBase, and verified by luciferase reporter assay. The level of FOXK1 was assessed by western blot. Results Increased expression of PART1 and FOXK1 was observed in OC tissues or cells, whereas miR-503-5p was downregulated. PART1 silencing or miR-503-5p overexpression repressed the cell viability, migration and invasion, and protomed apoptosis. Meanwhile, miR-503-5p was a target of PART1, and FOXK1 was a direct target gene of miR-503-5p. Both downregulation of miR-503-5p and upregulation of FOXK1 partly relieved the suppressive effects of PART1 knockdown on the oncogenicity of OC in vitro. Conclusion Decreased PART1 represses the cell viability, migration and invasion of OC via regulating the miR-503-5p/FOXK1 axis, which provided an underlying target for treating OC.