Long Noncoding RNA AB074169 Inhibits Cell Proliferation via Modulation of KHSRP-Mediated CDKN1a Expression in Papillary Thyroid Carcinoma

被引：89

作者：

Gou, Qiheng ^{[1
,2
]}

Gao, Linbo ^{[3
]}

Nie, Xinwen ^{[4
]}

Pu, Wenchen ^{[1
]}

Zhu, Jingqiang ^{[5
]}

Wang, Yichao ^{[5
]}

Liu, Xuesha ^{[1
]}

Tan, Shuangyan ^{[1
]}

Zhou, Jian-Kang ^{[1
]}

Gong, Yanqiu ^{[1
]}

He, Juan ^{[1
]}

Wu, Ke ^{[1
]}

Xie, Yuxin ^{[1
]}

Zhao, Wanjun ^{[5
]}

Dai, Lunzhi ^{[1
]}

Liu, Lunxu ^{[1
]}

Xiang, Rong ^{[6
]}

Wei, Yu-Quan ^{[1
]}

Zhang, Lin ^{[3
]}

Peng, Yong ^{[1
]}

机构：

[1] Sichuan Univ, State Key Lab Biotherapy, Dept Thorac Surg, Collaborat Innovat Ctr Biotherapy,West China Hosp, Chengdu, Sichuan, Peoples R China

[2] Sichuan Univ, West China Hosp, Dept Head & Neck Canc, Chengdu, Sichuan, Peoples R China

[3] Sichuan Univ, West China Univ Hosp 2, Key Lab Birth Defects & Related Dis Women & Child, Lab Mol & Translat Med,Minist Educ, Chengdu, Sichuan, Peoples R China

[4] Guangxi Univ Tradit Chinese Med, Dept Immunol & Microbiol, Nanning, Peoples R China

[5] Sichuan Univ, West China Hosp, Dept Thyroid Surg, Chengdu, Sichuan, Peoples R China

[6] Nankai Univ, Sch Med, Dept Clin Med, Tianjin, Peoples R China

来源：

CANCER RESEARCH | 2018年 / 78卷 / 15期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

KSRP CONTROLS; CANCER; GENE; DECAY; MIGRATION; PROMOTES; LNCRNAS;

D O I：

10.1158/0008-5472.CAN-17-3766

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Long noncoding RNAs (lncRNA) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here, we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell-cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. Significance: These findings identify a tumor-suppressive long noncoding RNA in papillary thyroid carcinoma. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/15/4163/F1.large.jpg. Cancer Res; 78(15); 4163-74. (C) 2018 AACR.

引用

页码：4163 / 4174

页数：12

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