Linc RNA ‐p21 suppresses development of human prostate cancer through inhibition of PKM 2

Objectives Previously, we found that long intergenic non‐coding RNA ‐p21 (linc RNA ‐p21) inhibited the development of human prostate cancer. However, the underlying molecular mechanisms are poorly understood. Here, we attempted to investigate the downstream targets of linc RNA ‐p21 in prostate cancer. Materials and methods Expression of lincRNA‐p21 and PKM2 was determined by qRT‐ PCR and Western blot. Lentivirus expressing shPKM2 or shCtrl was used to explore the role of PKM2 on the enhanced cell proliferation and glycolysis of linc RNA ‐p21‐silenced prostate cancer cells. A xenograft mouse model was performed to investigate the effect of PKM2 suppression, glycolytic or mammalian target of rapamycin (mTOR) inhibitor on the tumorigenic capacity of lincRNA‐p21‐silenced prostate cancer cells. Results We revealed that linc RNA ‐p21 silencing in DU 145 and LNC aP cells induced up‐regulation of PKM 2 and activation of glycolysis, which could be reversed by PKM 2 knockdown or rapamycin treatment. We also found that the proliferation and tumorigenesis of linc RNA ‐p21‐silenced prostate cancer cells were significantly inhibited after knocking down PKM 2. 3‐bromopyruvate (3‐Brpa) or rapamycin treatment largely decreased the tumour burden. Importantly, PKM 2 expression was inversely correlated with the linc RNA ‐p21 level and the survival of prostate cancer patients. Conclusions We demonstrated that linc RNA ‐p21 blunted the prostate cancer cell proliferation and tumorigenic capacity through down‐regulation of PKM 2. Therefore, targeting PKM 2 or glycolysis might be a therapeutic strategy in prostate cancer patients with lowly expressed linc RNA ‐p21.