Purpose: In order to investigate the role of miR-15b-5b in the progression of prostate cancer.
Methods: We employed RT-qPCR assay to analyze the transcriptional level of miR-15b-5b in cell lines including PC-3, prostate cancer tissues as well as normal prostate tissues. The protein level of large tumor suppressor factor 2 (LATS2) was detected by Western blot in similar specimens. Bioinformatic analysis was used to predict the targets of miR-15b-5p, and dual-luciferase assay was performed to confirm the relationship of miR-15b-5p with LATS2. Cell proliferation assay and colony formation assay were used to assess the effects of miR-15b-5b on the proliferation of PC-3 cells. Multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model.
Results: MiR-15b-5b was up-regulated in prostate cancer tissues as well as cell lines, and increased expression of miR-15b-5b was highly correlated with the poor prognosis of patients with prostate cancer. Ectopic expression of miR-15b-5b promoted the proliferation of PC-3 cells. Reciprocally, silence of miR-15b-5b elicited opposite effects on cell proliferation. Mechanistically, we identified LATS2 as the target of miR-15b-5b, which in turn limited LATS2 expression in PC-3 cells. Furthermore, the stimulatory effects of miR-15b-5b on cell proliferation can be attenuated by overexpression of LATS2. Conversely, inhibition of LATS2 promoted the proliferation of PC-3 cells induced by miR-15b-5b. Our data thus demonstrate that dysregulation of miR-15b-5b exacerbates prostate cancer progression via suppression of LATS2.
Conclusion: The identification of the oncogenic role of miR-15b-5b in prostate cancer thus proposes that miR-15b-5p might be a new therapeutic target for the treatment of prostate cancer.
Keywords: prostate cancer, miR-15b-5b, LATS2, proliferation