期刊
CELL PROLIFERATION
卷 50, 期 6, 页码 -出版社
WILEY
DOI: 10.1111/cpr.12395
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资金
- National Natural Science Foundation of China [81300625]
- Shanghai Science and Technology Committee [13DZ1940602]
- Shanghai Municipal Commission of Health and Family Planning [20134423]
Objectives: Previously, we found that long intergenic non-coding RNA-p21 (lincRNA-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 lincRNA-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 lincRNA-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 lincRNA-p21 silencing in DU145 and LNCaP cells induced up-regulation of PKM2 and activation of glycolysis, which could be reversed by PKM2 knockdown or rapamycin treatment. We also found that the proliferation and tumorigenesis of lincRNA-p21-silenced prostate cancer cells were significantly inhibited after knocking down PKM2. 3-bromopyruvate (3-Brpa) or rapamycin treatment largely decreased the tumour burden. Importantly, PKM2 expression was inversely correlated with the lincRNA-p21 level and the survival of prostate cancer patients. Conclusions: We demonstrated that lincRNA-p21 blunted the prostate cancer cell proliferation and tumorigenic capacity through down-regulation of PKM2. Therefore, targeting PKM2 or glycolysis might be a therapeutic strategy in prostate cancer patients with lowly expressed lincRNA-p21.
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