Downregulation of long noncoding RNA TUSC7 promoted cell growth, invasion and migration through sponging with miR-616-5p/GSK3β pathway in ovarian cancer

卵巢癌 癌症研究 下调和上调 免疫印迹 细胞生长 生物 竞争性内源性RNA 癌症 长非编码RNA 基因敲除 小RNA 细胞 环状RNA 基因沉默 Wnt信号通路 细胞周期 肿瘤科 细胞迁移 癌基因 小干扰RNA 转移 细胞凋亡 细胞培养 核糖核酸 反义RNA 内科学 医学 基因 遗传学
作者
Zhu Lm,Li N
出处
期刊:DOAJ: Directory of Open Access Journals - DOAJ 被引量:4
标识
DOI:10.26355/eurrev_202007_21880
摘要

Objective Long non-coding RNAs (lncRNAs) can serve as prognostic markers for cancer patients, including ovarian cancer. The objective of this study was to explore the potential functions and mechanisms of lncRNA-TUSC7 in ovarian cancer. Patients and methods RT-PCR or Western blot (WB) was performed to detect expressions of TUSC7, miR-616-5p and GSK3β in ovarian cancer tissues, adjacent normal tissues and ovarian cancer cell lines. Correlation analysis was performed to analyze the correlations between TUSC7 and miR-616-5p, miR-616-5p and GSK3β, TUSC7 and GSK3β. Furthermore, Kaplan-Meier survival analysis was used to analyze overall survival (OS) of patients with TUSC7 low and high expression. Besides, CCK-8 assay was carried out to measure cell proliferation ability and transwell assay was used to measure cell invasion and migration abilities. In addition, WB was performed to measure protein levels in ovarian cancer tissues and ovarian cancer cell lines. Finally, Luciferase reporter assay was performed to verify the binding sites between TUSC7 and miR-616-5p, miR-616-5p and GSK3β. Results In this study, we first found that TUSC7 was significantly reduced in ovarian cancer tissues, which was associated with advanced stage and poor diagnosis for ovarian cancer patients. MiR-616-5p was increased in ovarian cancer tissues and cancer cell lines, which was negatively correlated with TUSC7 and GSK3β. GSK3β was found to be reduced in ovarian cancer tissues, which was positively correlated with TUSC7. Of note, we found that TUSC7 overexpression inhibited cell proliferation, invasion and migration in SKOV3 cells. Moreover, protein expressions of Cyclin D1, N-cadherin, Vimentin, MMP-9 and MMP-2 were also repressed. Notably, Luciferase reporter assay proved that TUSC7 could directly sponge with miR-616-5p, which could directly bind with GSK3β, a tumor suppressor, regulating the β-catenin signaling. Finally, we proved that TUSC7 regulated cell proliferation, invasion and migration via miR-616-5p/GSK3β signaling pathway in SKOV3 cells. Conclusions According to the results, our study revealed that TUSC7 was repressed in patients with ovarian cancer, which might be used as a prognostic factor for ovarian cancer patients. Furthermore, we first discovered that the reduced TUSC7 promoted cell proliferation, invasion and migration of ovarian cancer via miR-616-5p/GSK3β/β-catenin pathway, which might provide a novel promising therapeutic target for ovarian cancer.
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