Long non‑coding RNA ASAP1‑IT1 suppresses ovarian cancer progression by regulating Hippo/YAP signaling

长链非编码 RNA ASAP1-IT1 通过调节 Hippo/YAP 信号抑制卵巢癌进展

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作者:Ke Wang, Yu-Bo Hu, Ye Zhao, Cong Ye

Abstract

Long non‑coding RNAs (lncRNAs) are a class of non‑protein coding transcripts that are involved in the regulation of gene expression in mammalian cells. Transcriptional co‑activator Yes associated protein 1 (YAP1) plays a key role in the progression of ovarian cancer. However, the regulation of Hippo/YAP signaling in ovarian cancer remains elusive. In the present study, the expression levels of lncRNA ASAP1‑IT1 were investigated. The analysis indicated that lncRNA ASAP1‑IT1 expression was downregulated in ovarian tumor samples and ovarian cancer cells. The overexpression of ASAP1‑IT1 inhibited ovarian cancer cell proliferation and induced cell apoptosis. Bioinformatics analysis predicted that miR‑2278, a previously reported upregulated miRNA in ovarian tumors, may bind to ASAP1‑IT1. Dual luciferase assay confirmed the direct regulatory association between ASAP1‑IT1 and miR‑2278. In addition, the data demonstrated that large tumor suppressor 2 (LATS2) was a target gene of miR‑2278, whose expression was upregulated by ASAP1‑IT1 in ovarian cancer cells. By regulating the expression of LATS2, ASAP1‑IT1 induced the downregulation of YAP1 expression in ovarian cancer cells. Moreover, the silencing of LATS2 attenuated the inhibition of cell proliferation and the apoptosis induced by ASAP1‑IT1 overexpression in ovarian cancer cells. The association among the expression levels of ASAP1‑IT1, miR‑2278 and LATS2 was observed in specimens obtained from patients with ovarian cancer. Taken together, the data presented herein demonstrate that ASAP1‑IT1 functions as a potential tumor suppressor lncRNA by upregulating LATS2 expression in ovarian cancer.

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