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LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis.

Research paper by Jin-Tian JT Miao, Jian-Hua JH Gao, Yong-Qian YQ Chen, Hong H Chen, Hao-Yi HY Meng, Ge G Lou

Indexed on: 15 Feb '20Published on: 14 Jun '19Published in: Bioscience Reports



Abstract

This paper tried to explore ANRIL expression in ovarian cancer and how it affects cisplatin-sensitivity of ovarian cancer cells via regulation of let-7a/HMGA2 axis. qRT-PCR was used to detect ANRIL and let-7a levels in ovarian cancer tissues and cell lines (SKOV3 and SKOV3/DDP). Then cells were randomly assigned into Blank, NC siRNA, ANRIL siRNA, let-7a inhibitor, and ANRIL siRNA+let-7a inhibitor groups. CCK-8 assay was applied for assessing cell viability of cells treated with different concentrations of cisplatin . Flow cytometry was employed to test cell apoptosis rate. QRT-PCR and Western blot were performed for related-molecules detection. Nude mice transplanted with SKOV3/DDP cells were used to confirm the effects of ANRIL siRNA on the cisplatin-sensitivity. Ovarian cancer tissues and cisplatin-resistant cells had increased ANRIL expression and decreased let-7a expression, and those patients with higher clinical stage and pathological grade showed higher ANRIL and lower let-7a. Dual-luciferase reporter gene assay confirmed the targeting relationship between ANRIL and let-7a, and between let-7a and HMGA2. The cell viability and cisplatin IC were decreased in ANRIL siRNA group exposed to different concentrations of cisplatin, with enhanced apoptosis, as well as elevated let-7a and declined HMGA2, which would be reversed by let-7a inhibitor. Meanwhile, ANRIL down-regulation enhanced the inhibitory effect of cisplatin on tumor growth of nude mice and reduced tumor weight. Silencing ANRIL expression reduced HMGA2 expression to promote the apoptosis and improve cisplatin-sensitivity of ovarian cancer cells via up-regulating let-7a expression. ©2019 The Author(s).