title: Identification of microRNA-98 as a therapeutic target inhibiting prostate cancer growth and a biomarker induced by vitamin D.
abstract: The anti-tumor effect of vitamin D has been well recognized but its translational application is hindered by side effects induced by supra-physiological concentration of vitamin D required for cancer treatment. Thus, exploring the vitamin D tumor suppressive functional mechanism can facilitate improvement of its clinical application. We screened miRNA profiles in response to vitamin D and found that a tumor suppressive miRNA, miR-98, is transcriptionally induced by 1α,25-dihydroxyvitamin D(3) (1,25-VD) in LNCaP. Mechanistic dissection revealed that 1,25-VD-induced miR-98 is mediated through both a direct mechanism, enhancing the VDR binding response element in the promoter region of miR-98, and an indirect mechanism, down-regulating LIN-28 expression. Knockdown of miR-98 led to a reduction of 1,25-VD anti-growth effect and overexpression of miR-98 suppressed the LNCaP cells growth via inducing G2/M arrest. And CCNJ, a protein controlling cell mitosis, is down-regulated by miR-98 via targeting 3'-untranslated region of CCNJ. Interestingly, miR-98 levels in blood are increased upon 1,25-VD treatment in mice suggesting the biomarker potential of miR-98 in predicting 1,25-VD response. Together, the finding that growth inhibitive miR-98 is induced by 1,25-VD provides a potential therapeutic target for prostate cancer and a potential biomarker for 1,25-VD anti-tumor action.
authors.affiliation: Department of Urology, University of Rochester, Rochester, New York 14642, USA.
authors.forename: Huei-Ju
authors.initials: HJ
authors.lastname: Ting
authors.forename: James
authors.initials: J
authors.lastname: Messing
authors.forename: Sayeda
authors.initials: S
authors.lastname: Yasmin-Karim
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Lee
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011485:Protein Binding; D014158:Transcription, Genetic; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C546084:MIRN98 microRNA, human; D035683:MicroRNAs; D014807:Vitamin D