Long intragenic non-coding RNA lincRNA-p21 suppresses development of human prostate cancer.

Abstract

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.