Circ_0002762 Regulates Oncoprotein YBX1 in Cervical Cancer via mir-375 to Regulate the Malignancy of Cancer Cells.

BACKGROUND: Cervical carcinoma (CC) is the third most common cancer among females and the fourth leading cause of cancer-related death, which poses a serious threat to women's health. This study investigated the biological function and mechanism of circRNA circ_0002762 in the malignant progression of CC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_0002762, microRNA-375 (miR-375) and Y-box binding protein 1 (YBX1) mRNA expressions in CC tissues and cell lines. After circ_0002762 was overexpressed in CC cell lines, cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and wound healing assays were executed to probe cell growth and migration. Additionally, the targeting relationships between miR-375 and circ_0002762 or YBX1 3'-UTR were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Western blot was adopted to examine YBX1 protein levels in CC cells. RESULTS: Circ_0002762 expression was raised in CC tissues and cell lines, and highly expressed circ_0002762 was associated with larger tumor size and lymph node metastasis of CC patients. Circ_0007262 overexpression markedly accelerated the proliferation and migration of CC cells. Besides, miR-375 was revealed to be a downstream target of circ_0002762, and miR-375 overexpression counteracted the promoting effects of circ_0002762 overexpression on CC cell viability and migration. YBX1 was identified as a target of miR-375, and circ_0002762 positively modulated YBX1 expressions through adsorbing miR-375. CONCLUSION: Circ_0002762 promotes the progression of CC via sponging miR-375 and up-regulating YXB1 expression.

PD98059 impairs the cisplatin-resistance of ovarian cancer cells by suppressing ERK pathway and epithelial mesenchymal transition process.

BACKGROUND: The study was aimed at investigating the role of PD98059 on impairing the cisplatin-resistance of ovarian cancer cells and figuring out the potential mechanism. MATERIAL AND METHODS: Treated with low dose of cisplatin (DDP), DDP-resistant ovarian cancer cells were built and named as SKOV-3/DDP. The cell viabilities of ovarian cancer cell line SKOV-3 and SKOV-3/DDP were detected using MTT assay. Wound healing assay and flow cytometry were performed to detect the migratory ability and cell cycle variation of the two cells and assess the sensibility to DDP in the two cell lines. However, cotreated with DDP and PD98059, cell viability, migration and cell cycle of SKOV-3/DDP were determined again. The DDP-resistance varied a lot and the potential mechanism was studied via western blot assay. RESULTS: Both treated with DDP, SKOV-3/DDP showed an intense resistance than SKOV-3 including stronger cell viability, larger migration area and less G1/G0 arrest, which confirmed the successfully established DDP-resistant cell line. The phosphorylation of ERK and the activation of epithelial mesenchymal transition (EMT) process contributes to the enhanced resistance. PD98059, a MEK inhibitor, suppresses the ERK pathway and the EMT process of SKOV-3/DDP. Co-treated by DDP and PD98059, cell proliferation and migratory area decreased, meantime more cell were arrested in G0/G1 phase compared to simple treatment of DDP or PD98059. CONCLUSION: PD98059 efficiently impairs the DDP-resistance of ovarian cancer cells via downregulating the ERK pathway and the EMT process.