LncRNA CASC15 Functions As An Unfavorable Predictor Of Ovarian Cancer Prognosis And Inhibits Tumor Progression Through Regulation Of miR-221/ARID1A Axis

Yin Shi; Shanshan Gao; Ying Zheng; Mukun Yao; Fan Ruan

doi:10.2147/OTT.S219900

LncRNA CASC15 Functions As An Unfavorable Predictor Of Ovarian Cancer Prognosis And Inhibits Tumor Progression Through Regulation Of miR-221/ARID1A Axis

Onco Targets Ther. 2019 Oct 23:12:8725-8736. doi: 10.2147/OTT.S219900. eCollection 2019.

Authors

Yin Shi¹, Shanshan Gao¹, Ying Zheng¹, Mukun Yao¹, Fan Ruan¹

Affiliation

¹ Department of Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People's Republic of China.

Abstract

Background: LncRNA cancer susceptibility candidate 15 (CASC15) has been demonstrated to act as an oncogene in different cancers; however, its role in ovarian cancer remains elusive.

Methods: Quantitative real-time PCR (qRT-PCR) was performed to examine the expression of lncRNA CASC15. Kaplan-Meier survival analysis was performed to evaluate the prognostic significance of lncRNA CASC15. CCK-8, soft-agar colony-formation, flow cytometry, transwell migration and invasion assays were used to analyze the biological behavior of lncRNA CASC5 in ovarian cancer. Furthermore, the potential mechanism of lncRNA CAC15 was investigated by bioinformatics analysis, luciferase reporter assay, and biotin pull-down assay.

Results: In this study, we found that the expression of CASC15 was lower in ovarian cancer tissues and cells by qRT-PCR. In addition, low expression of CASC15 was closely correlated with advanced TNM stage, moderate/poor differentiation, and larger size. Moreover, Kaplan-Meier survival analysis showed that patients with low CASC15 expression level had poorer overall survival and progression-free survival than those with high CASC15 expression. Meanwhile, ROC analysis found that CASC15 had diagnostic values to distinguish tumor tissues from nontumorous tissues. Overexpression of CASC15 prohibited the malignancy of ovarian cancer cells, including proliferation, colony formation, cell cycle, migration, and invasion, and promoted cell apoptosis. In addition, bioinformatics analysis, luciferase reporter assay, and biotin pull-down assay confirmed that CASC15 straightly interacted with miR-221. We also observed that ARID1A was a downstream target of miR-221 and CASC15 subsequently exerted its tumor-suppressive effects by regulating the expression of ARID1A in ovarian cancer cells.

Conclusion: Overall, this study firstly elucidated that CASC15 could play a tumor-suppressive role in ovarian cancer by the regulation of CASC15/miR-221/ARID1A axis, which may provide a ponderable prognostic biomarker and promising therapeutic target for treatment of patients with ovarian cancer.

Keywords: ARID1A; CASC15; long non-coding RNA; miR-221; ovarian cancer.