title: miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 by directly targeting E2F3 in gastric cancer cells.
abstract: VitaminD3 signaling is involved in inhibiting the development and progression of gastric cancer (GC), while the active vitamin D metabolite 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)-mediated gene regulatory mechanisms in GC remain unclear. We found that miR-145 is induced by 1,25(OH)2D3 in a dose- and vitamin D receptor (VDR)-dependent manner in GC cells. Inhibition of miR-145 reverses the antiproliferative effect of 1,25(OH)2D3. Furthermore, miR-145 expression was lower in tumors compared with matched normal samples and correlated with increased the E2F3 transcription factor protein staining. Overexpression of miR-145 inhibited colony formation, cell viability and induced cell arrest in S-phase in GC cells by targeting E2F3 and CDK6. miR-145 inhibition consistently abrogates the 1,25(OH)2D3-mediated suppression of E2F3, CDK6, CDK2 and CCNA2 genes. Altogether, our results indicate that miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Su'e
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.|Department of Oral Maxillofacial Surgery, Stomatology Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Tong
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Liying
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Tusheng
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Genetics and Molecular Biology/Key Laboratory of Environment and Genes Related to Diseases, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D050699:E2F3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D018167:Receptors, Calcitriol; D002117:Calcitriol
keywords: 1,25(OH)2D3; E2F3; gastric cancer; miR-145; proliferation