The long non-coding RNA ANRIL promotes proliferation and cell cycle progression and inhibits apoptosis and senescence in epithelial ovarian cancer.
Antisense non-coding RNA in the INK4 locus (ANRIL) has been implicated in a variety of cancers. In the present study, we evaluated ANRIL expression in epithelial ovarian cancer (EOC) and defined its clinical implications and biological functions. ANRIL was overexpressed in EOC tissues relative to normal controls. Overexpression correlated with advanced International Federation of Gynecologists and Obstetricians stage and high histological grade. Multivariate analysis indicated that ANRIL is an independent prognostic factor for overall survival in EOC. Gain- and loss-of-function experiments demonstrated that ANRIL promotes EOC cell proliferation both in vitro and in vivo. The proliferative effect was linked to the promotion of cell cycle progression and inhibition of apoptosis and senescence. Down-regulation of P15INK4B and up-regulation of Bcl-2 by ANRIL may partially explain ANRIL-induced EOC cell proliferation. This study is the first to establish that ANRIL promotes EOC progression and is a potential prognostic biomarker.
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.|Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
Jun-Jun
JJ
Qiu
Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Yan
Y
Wang
Department of Gynecology, The Second Affiliated Hospital of Nantong University, Nantong, China.
Ying-Lei
YL
Liu
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.|Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
Ying
Y
Zhang
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.|Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
Jing-Xin
JX
Ding
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.|Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
Ke-Qin
KQ
Hua
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D015996:Survival Rate
C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding
ANRIL; apoptosis; cell cycle; proliferation; senescence