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

L.-M. Zhu, N. Li

Department of Maternal and Child Health Promotion, Department of Obstetrics Yantai Affiliated Hospital, Binzhou Medical College, Yantai City, Shandong Province, China. Lining0916@qq.com

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• Oncology

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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