title: MiR199b suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in prostate cancer cells.
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.
authors.affiliation: Laboratory of Pathology, State Key Laboratory of Biotherapy and Department of Pathology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. zhouqiao@mcwcums.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shang
authors.forename: Xueqin
authors.initials: X
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Nie
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Zeng
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D016923:Cell Death; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012323:RNA Processing, Post-Transcriptional; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D035683:MicroRNAs; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C531408:mirn199 microRNA, human