Wang Xiaohai, Ruan Yuan, Wang Xingjie, Zhao Wei, Jiang Qi, Jiang Chenyi, Zhao Yuyang, Xu Yongzhi, Sun Feng, Zhu Yiping, Xia Shujie, Xu Dongliang
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Cell Prolif. 2017 Apr;50(2). doi: 10.1111/cpr.12318. Epub 2016 Dec 14.
Prostate cancer is one of the most frequent malignancies in men, worldwide, although its underlying mechanisms are not fully understood. Long non-coding RNAs participate in development of human cancers. In this invetsigation, we aimed to study the roles of lincRNA-p21 in development of human prostate cancer.
Expression of lincRNA-p21 was assessed by real-time PCR in cell lines and in human tissues. Lentivirus carrying sh-lincRNA-p21, lincRNA-p21 or control constructs were used to determine their effects on cell proliferation and apoptosis. A mouse xenograft model was employed to explore the functions of lincRNA-p21 on cancer cell population growth in vivo. Relationships between p53 downstream genes and lincRNA-p21 levels were explored by real-time PCR, western blotting and chromatin immunoprecipitation.
LincRNA-p21 was found to be down-regulated in human prostate cancer, and low levels of lincRNA-p21 correlated with high disease stage and prediction of poor survival. We further showed that lincRNA-p21 inhibited prostate cancer cell proliferation and colony formation in vitro and reduced rate of prostate cancer cell population growth in vivo. Study of mechanisms involved revealed that lincRNA-p21 promoted apoptosis and induced expression of p53 downstream genes by regulating p53 binding to their promoters. Finally, we showed that expression of p53 downstream genes was reduced in the malignant prostate tissues, which correlated with lincRNA-p21 level.
Our findings indicated that lincRNA-p21 inhibited development of human prostate cancer partly by regulating p53 downstream gene expression and partly by apoptotic activation.
前列腺癌是全球男性中最常见的恶性肿瘤之一，但其潜在机制尚未完全明确。长链非编码RNA参与人类癌症的发生发展。在本研究中，我们旨在探讨lincRNA-p21在人类前列腺癌发生发展中的作用。
通过实时定量PCR检测细胞系和人体组织中lincRNA-p21的表达。使用携带sh-lincRNA-p21、lincRNA-p21或对照构建体的慢病毒来确定它们对细胞增殖和凋亡的影响。采用小鼠异种移植模型探讨lincRNA-p21在体内对癌细胞群体生长的作用。通过实时定量PCR、蛋白质免疫印迹法和染色质免疫沉淀法研究p53下游基因与lincRNA-p21水平之间的关系。
发现lincRNA-p21在人类前列腺癌中表达下调，低水平的lincRNA-p21与高疾病分期及不良生存预后相关。我们进一步表明，lincRNA-p21在体外抑制前列腺癌细胞增殖和集落形成，并在体内降低前列腺癌细胞群体生长速率。对相关机制的研究表明，lincRNA-p21通过调节p53与其启动子的结合来促进细胞凋亡并诱导p53下游基因的表达。最后，我们发现恶性前列腺组织中p53下游基因的表达降低，这与lincRNA-p21水平相关。
我们的研究结果表明，lincRNA-p21部分通过调节p53下游基因表达，部分通过激活凋亡来抑制人类前列腺癌的发展。
