Xi Jie, Feng Jing, Li Qian, Li Xia, Zeng Saitian
Department of Gynecology, Cangzhou Central Hospital, Cangzhou, Heibei 061001, P.R. China.
Int J Oncol. 2017 May;50(5):1663-1670. doi: 10.3892/ijo.2017.3933. Epub 2017 Mar 24.
Breast cancer, one of the common cancers of women, is the leading cause of death among women below the age of 50 years in western countries. Long non-coding RNAs (lncRNAs) have been shown to be involved in diverse biological processes, both physical and pathological. However, to date, only a few lncRNAs have been functionally identified in breast cancer, and the overall pathophysiological contributions of lncRNAs to breast cancer remain largely unknown. In the present study, we identified a novel lncRNA termed lncFOXO1 through microarray screening. lncFOXO1 is significantly decreased in breast cancer tissues and cell lines and downregulation of lncFOXO1 expression associates with poorer overall survival. Functional assays demonstrated its suppressive role in breast cancer in vivo and in vitro. Mechanistically, lncFOXO1 suppressed the growth of breast cancer by increasing FOXO1 transcription. Moreover, we found that lncFOXO1 associated with BRCA-1-associated protein 1 (BAP1) and regulates its binding and the level of mono-ubiquitinated H2A at K119 (ubH2AK119) at FOXO1 promoter.
乳腺癌是女性常见癌症之一,在西方国家是50岁以下女性的主要死因。长链非编码RNA(lncRNA)已被证明参与多种生理和病理生物学过程。然而,迄今为止,在乳腺癌中仅功能性鉴定出少数lncRNA,lncRNA对乳腺癌的整体病理生理贡献仍 largely未知。在本研究中,我们通过微阵列筛选鉴定出一种名为lncFOXO1的新型lncRNA。lncFOXO1在乳腺癌组织和细胞系中显著降低,lncFOXO1表达下调与较差的总生存期相关。功能试验证明了其在体内和体外对乳腺癌的抑制作用。机制上,lncFOXO1通过增加FOXO1转录来抑制乳腺癌生长。此外,我们发现lncFOXO1与BRCA-1相关蛋白1(BAP1)相关,并调节其在FOXO1启动子处的结合以及K119处单泛素化H2A(ubH2AK119)的水平。