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MiR199b Suppresses Expression of Hypoxia-Inducible Factor 1α (HIF-1α) in Prostate Cancer Cells
Laboratory of Pathology, State Key Laboratory of Biotherapy and Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China
* Author to whom correspondence should be addressed.
Received: 17 February 2013; in revised form: 8 April 2013 / Accepted: 10 April 2013 / Published: 17 April 2013
Abstract: MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally repress expression of target genes via imperfect base-pairing with the 3'-untranslated region (3'-UTR). The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays important roles in physiology and pathology. Constitutive over-expression of HIF-1α is observed in many types of cancers including prostate carcinoma, but the mechanisms underlying this event remain largely unknown. Here we investigated the expression of miR199b and HIF-1α in normal prostate tissue, prostate cancer tissues and prostate carcinoma (PCa) cell lines LNCaP, PC-3 and DU145.We found that miR-199b expression level was decreased in prostate cancer while HIF-1α was significantly over-expressed. Furthermore, we postulated the posttranscriptional regulation of HIF-1α by miR199b through bioinformatics analysis, and herein we experimentally demonstrated that miR199b negatively regulated HIF-1α by targeting its 3'-untranslated region. Artificial over-expression of miR199b by using adenoviral vectors in prostate cancer PC-3 and DU145 cells significantly down-regulated HIF-1α, together with reduced cell growth and increased cell death.
Keywords: miR-199b; HIF-1α; prostate cancer
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Shang, W.; Chen, X.; Nie, L.; Xu, M.; Chen, N.; Zeng, H.; Zhou, Q. MiR199b Suppresses Expression of Hypoxia-Inducible Factor 1α (HIF-1α) in Prostate Cancer Cells. Int. J. Mol. Sci. 2013, 14, 8422-8436.
Shang W, Chen X, Nie L, Xu M, Chen N, Zeng H, Zhou Q. MiR199b Suppresses Expression of Hypoxia-Inducible Factor 1α (HIF-1α) in Prostate Cancer Cells. International Journal of Molecular Sciences. 2013; 14(4):8422-8436.
Shang, Weiwei; Chen, Xueqin; Nie, Ling; Xu, Miao; Chen, Ni; Zeng, Hao; Zhou, Qiao. 2013. "MiR199b Suppresses Expression of Hypoxia-Inducible Factor 1α (HIF-1α) in Prostate Cancer Cells." Int. J. Mol. Sci. 14, no. 4: 8422-8436.