Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma

被引：63

作者：

Peng, Haoran ^{[1
]}

Ishida, Masaharu ^{[1
]}

Li, Ling ^{[1
]}

Saito, Atsushi ^{[2
]}

Kamiya, Atsushi ^{[2
]}

Hamilton, James P. ^{[1
]}

Fu, Rongdang ^{[3
]}

Olaru, Alexandru V. ^{[1
]}

An, Fangmei ^{[4
]}

Popescu, Irinel ^{[5
]}

Iacob, Razvan ^{[5
]}

Dima, Simona ^{[5
]}

Alexandrescu, Sorin T. ^{[5
]}

Grigorie, Razvan ^{[5
]}

Nastase, Anca ^{[5
]}

Berindan-Neagoe, Ioana ^{[6
,7
,8
]}

Tomuleasa, Ciprian ^{[8
,9
]}

Graur, Florin ^{[10
,11
]}

Zaharia, Florin ^{[10
,11
]}

Torbenson, Michael S. ^{[12
]}

Mezey, Esteban ^{[1
]}

Lu, Minqiang ^{[3
]}

Selaru, Florin M. ^{[1
,13
]}

机构：

[1] Johns Hopkins Univ Hosp, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA

[3] Sun Yat Sen Univ, Affiliated Hosp 3, Liver Transplantat Ctr, Guangzhou 510275, Guangdong, Peoples R China

[4] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Gastroenterol, Wuxi, Jiangsu, Peoples R China

[5] Dan Setlacec Ctr Gen Surg & Liver Transplantat, Fundeni Clin Inst, Bucharest, Romania

[6] Iuliu Hatieganu Univ Med & Pharm, Dept Immunol, Cluj Napoca, Romania

[7] Oncol Inst Ion Chiricuta, Dept Funct Genom, Cluj Napoca, Romania

[8] Iuliu Hatieganu Univ Med & Pharm, Res Ctr Funct Genom Biomed & Translat Med, Cluj Napoca, Romania

[9] Oncol Inst Ion Chiricuta, Dept Hematol, Cluj Napoca, Romania

[10] Iuliu Hatieganu Univ Med & Pharm, Dept Surg, Cluj Napoca, Romania

[11] Reg Inst Gastroenterol & Hepatol Octavian Fodor, Dept Surg, Cluj Napoca, Romania

[12] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA

[13] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA

来源：

ONCOTARGET | 2015年 / 6卷 / 08期

基金：

中国国家自然科学基金;

关键词：

hepatocellular carcinoma; pseudogene; tumor suppressor; competitive endogenous RNA; INTS6; LONG NONCODING RNA; MOLECULAR CHARACTERIZATION; PROSTATE-CANCER; MESSENGER-RNAS; LIVER-CANCER; CELL-GROWTH; EXPRESSION; DICE1; MUTATIONS; LANDSCAPE;

D O I：

10.18632/oncotarget.3290

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The complex regulation of tumor suppressive gene and its pseudogenes play key roles in the pathogenesis of hepatocellular cancer (HCC). However, the roles played by pseudogenes in the pathogenesis of HCC are still incompletely elucidated. This study identifies the putative tumor suppressor INTS6 and its pseudogene INTS6P1 in HCC through the whole genome microarray expression. Furthermore, the functional studies - include growth curves, cell death, migration assays and in vivo studies - verify the tumor suppressive roles of INTS6 and INTS6P1 in HCC. Finally, the mechanistic experiments indicate that INTS6 and INTS6P1 are reciprocally regulated through competition for oncomiR-17-5p. Taken together, these findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p. Our investigation of this regulatory circuit reveals novel insights into the underlying mechanisms of hepatocarcinogenesis.

引用

页码：5666 / 5677

页数：12

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