Hypoxia induced upregulation of miR-301a/b contributes to increased cell autophagy and viability of prostate cancer cells by targeting NDRG2

Y.-J. Guo, J.-X. Liu, Y.-W. Guan

Department of Urology, General Hospital of Beijing Military Region, PLA, Beijing, China. yaweiguan1@tom.com

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• Oncology

OBJECTIVE: Previous studies reported that NDRG2 might be a tumor suppressor of prostate cancer. In this study, we investigated the hypoxia-induced expression change of miR-301a/b in prostate cancer cells and explored its regulation on NDRG2 in autophagy and viability of prostate cancer cells.

MATERIALS AND METHODS: MiR-301a/b expression in hypoxia and normoxia cultured prostate cancer cells was measured. Its regulation on autophagy was measured by quantifying expression change of LC3B and p62. The direct binding between miR-301a/b and 3’UTR of NDRG2 was verified using dual luciferase, qRT-PCR and Western blot assay. The influence of miR-301a/b-NDRG2 axis on autophagy, viability and apoptosis of prostate cancer cells was further investigated.

RESULTS: Hypoxia induced a significant upregulation of miR-301a/b in prostate cancer cells. Enhanced miR-301a/b expression significantly weakened autophagy of prostate cancer cells. Both miR-301a and miR-301b could directly target 3’UTR of NDRG2 and decrease its expression. Decreased NDRG2 expression directly resulted in increased autophagy and cell viability and reduced cell apoptosis.

CONCLUSIONS: Taken together, we demonstrated that miR-301a/b-NDRG2 might be an important axis modulating autophagy and viability of prostate cancer cells under hypoxia.

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