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
收藏
页码：4909 / 4921
页数：13
相关论文
共 30 条
[1]   The RNA Modification N6-methyladenosine and Its Implications in Human Disease [J].
Batista, Pedro J. .
GENOMICS PROTEOMICS & BIOINFORMATICS, 2017, 15 (03) :154-163
[2]  
Cao SH, 2014, INT J CLIN EXP PATHO, V7, P6776
[3]  
D'Angelo Edoardo, 2018, Noncoding RNA Res, V3, P174, DOI 10.1016/j.ncrna.2018.08.002
[4]  
Dong X, 2018, AM J CANCER RES, V8, P1414
[5]   LncRNA GAS5 confers the radio sensitivity of cervical cancer cells via regulating miR-106b/IER3 axis [J].
Gao, Junbi ;
Liu, Liya ;
Li, Gailing ;
Cai, Mingbo ;
Tan, Chaoyue ;
Han, Xiaoxiao ;
Han, Liping .
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, 2019, 126 :994-1001
[6]   Long Noncoding RNA EGFR-AS1 Promotes Cell Proliferation by Increasing EGFR mRNA Stability in Gastric Cancer [J].
Hu, Jiaojiao ;
Qian, Yingying ;
Peng, Lipan ;
Ma, Ling ;
Qiu, Tianzhu ;
Liu, Yiqian ;
Li, Xiao ;
Chen, Xiaofeng .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 49 (01) :322-334
[7]   The Critical Role of RNA m6A Methylation in Cancer [J].
Lan, Qing ;
Liu, Pei Y. ;
Haase, Jacob ;
Bell, Jessica L. ;
Huettelmaier, Stefan ;
Liu, Tao .
CANCER RESEARCH, 2019, 79 (07) :1285-1292
[8]   Sirt1 Antisense Long Noncoding RNA Promotes Cardiomyocyte Proliferation by Enhancing the Stability of Sirt1 [J].
Li, Bing ;
Hu, Yinlan ;
Li, Xinzhong ;
Jin, Guoqing ;
Chen, Xiaoqiang ;
Chen, Guojun ;
Chen, Yanmei ;
Huang, Senlin ;
Liao, Wangjun ;
Liao, Yulin ;
Teng, Zhonghua ;
Bin, Jianping .
JOURNAL OF THE AMERICAN HEART ASSOCIATION, 2018, 7 (21)
[9]   Amplification of Long Noncoding RNA ZFAS1 Promotes Metastasis in Hepatocellular Carcinoma [J].
Li, Tao ;
Xie, Junjie ;
Shen, Chuan ;
Cheng, Dongfeng ;
Shi, Yuan ;
Wu, Zhichong ;
Deng, Xiaxing ;
Chen, Hao ;
Shen, Baiyong ;
Peng, Chenghong ;
Li, Hongwei ;
Zhan, Qian ;
Zhu, Zhecheng .
CANCER RESEARCH, 2015, 75 (15) :3181-3191
[10]   lncRNA GAS5 Reverses EMT and Tumor Stem Cell-Mediated Gemcitabine Resistance and Metastasis by Targeting miR-221/SOCS3 in Pancreatic Cancer [J].
Liu, Bingyan ;
Wu, Shaoqiu ;
Ma, Jun ;
Yan, Shuo ;
Xiao, Zhengguang ;
Wan, Linhuang ;
Zhang, Feng ;
Shang, Mingyi ;
Mao, Aiwu .
MOLECULAR THERAPY-NUCLEIC ACIDS, 2018, 13 :472-482
123