Qiu Jun-Jun, Wang Yan, Liu Ying-Lei, Zhang Ying, Ding Jing-Xin, Hua Ke-Qin
Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, China.
Oncotarget. 2016 May 31;7(22):32478-92. doi: 10.18632/oncotarget.8744.
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.
INK4基因座中的反义非编码RNA（ANRIL）与多种癌症有关。在本研究中，我们评估了ANRIL在上皮性卵巢癌（EOC）中的表达，并明确了其临床意义和生物学功能。相对于正常对照，EOC组织中ANRIL过表达。过表达与国际妇产科联盟晚期分期和高组织学分级相关。多变量分析表明，ANRIL是EOC总生存的独立预后因素。功能获得和功能丧失实验表明，ANRIL在体外和体内均促进EOC细胞增殖。增殖作用与促进细胞周期进程以及抑制细胞凋亡和衰老有关。ANRIL导致P15INK4B下调和Bcl-2上调可能部分解释了ANRIL诱导的EOC细胞增殖。本研究首次证实ANRIL促进EOC进展，并且是一种潜在的预后生物标志物。
