Chen Na, Hu Taobo, Gui Yuanyuan, Gao Jieying, Li Zhihong, Huang Shi
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
PeerJ. 2019 May 15;7:e6941. doi: 10.7717/peerj.6941. eCollection 2019.
Bcl-2 (B-cell lymphoma 2) protein is localized in the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. PRDM10 is a member of the PR/SET family of epigenetic regulators and may play a role in development and cell differentiation. Here we show that human PRDM10 contributes to the transcriptional regulation of human Bcl-2 gene. We found that PRDM10-depletion in human cells reduced the expression of Bcl-2 protein and over-expression of PRDM10 promoted Bcl-2 protein expression. Furthermore, luciferase reporter activity of Bcl-2 gene P1 promoter was significantly increased in cells co-transfected with PRDM10, and PRDM10 was able to bind to the Bcl-2 P1 promoter . Using The Cancer Genome Atlas (TCGA) data set, we found weak positive correlation between PRDM10 and Bcl-2 in several cancer types including cancers of the breast, colon, and lung tissues. These data identify a novel function for PRDM10 protein and provide insights on the transcriptional control of Bcl-2 expression.
Bcl-2(B细胞淋巴瘤2)蛋白定位于线粒体的外膜,在促进细胞存活和抑制促凋亡蛋白的作用中发挥重要作用。PRDM10是表观遗传调节因子PR/SET家族的成员,可能在发育和细胞分化中起作用。在此我们表明,人类PRDM10有助于人类Bcl-2基因的转录调控。我们发现,人类细胞中PRDM10的缺失降低了Bcl-2蛋白的表达,而PRDM10的过表达促进了Bcl-2蛋白的表达。此外,在与PRDM10共转染的细胞中,Bcl-2基因P1启动子的荧光素酶报告活性显著增加,并且PRDM10能够与Bcl-2 P1启动子结合。使用癌症基因组图谱(TCGA)数据集,我们发现在包括乳腺癌、结肠癌和肺癌组织在内的几种癌症类型中,PRDM10与Bcl-2之间存在弱正相关。这些数据确定了PRDM10蛋白的一种新功能,并为Bcl-2表达的转录控制提供了见解。