Long noncoding RNA GAS5-AS1 suppresses growth and metastasis of cervical cancer by increasing GAS5 stability

被引：19

作者：

Wang, Xiao ^{[1
]}

Zhang, Junjun ^{[1
]}

Wang, Yan ^{[1
]}

机构：

[1] Henan Univ Sci & Technol, Affiliated Hosp 1, Dept Gynecol, Jinghua Rd, Luoyang 471003, Henan, Peoples R China

来源：

AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH | 2019年 / 11卷 / 08期

关键词：

RNA stability; m(6)A modification; ALKBH5; YTHDF2; TUMOR-SUPPRESSOR; PROMOTES; EXPRESSION; RESISTANCE;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cervical cancer (CC) is the second most common cancer and the fourth leading cause of cancer-related death in women worldwide. Up to date, only a few of long noncoding RNAs (lncRNAs) have been functionally characterized. Here, we aimed to discover the functional roles of lncRNA GAS5-AS1. The GAS5-AS1 expression in CC tissues was markedly decreased when compared with that in the adjacent normal tissues. The downregulation of GAS5-AS1 was significantly correlated with the advanced FIGO stage, distant metastasis, lymphatic metastasis and poor prognosis in patients with CC. Functionally, GAS5-AS1 drastically reduced CC cell proliferation, migration and invasion in vitro, and remarkably suppressed CC tumorigenicity and metastasis in vivo. Mechanistically, it was found that GAS5-AS1 interacted with the tumor suppressor GAS5, and increased its stability by interacting with RNA demethylase ALKBH5 and decreasing GAS5 N6-methyladenosine (m(6)A) modification. Moreover, it was shown that m(6)A-mediated GAS5 RNA degradation relied on the m(6)A reader protein YTHDF2-dependent pathway. Our findings reveal an important mechanism of epigenetic alteration in CC carcinogenesis and metastasis.

引用

页码：4909 / 4921

页数：13

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