title: Mutation R273H confers p53 a stimulating effect on the IGF-1R-AKT pathway via miR-30a suppression in breast cancer.
abstract: p53 is the most highly mutated tumor suppressor in human malignancies. A wide array of p53 mutations has been revealed to play pivotal roles during cancer progression, which abolish anti-tumor functions of wild type p53 but also elicit tumorigenic effects by activating a diverse subset of downstream molecules. R273H mutation of p53 has been closely implicated in human cancer. Here we report miR-30a as a novel downstream target of p53 R273H mutant, which binds to the promoter region to repress miR-30a expression. Consequently, p53 R273H mutant enhances the migratory capabilities of tumor cells that are compromised by exogenous miR-30a over-expression. Our further investigation indicates that p53 R273H mutation unleashes the inhibition effect of miR-30a on IGF-1R expression, thus leading to elevated activation of IGF-1R-AKT signaling cascade in tumor cells.
authors.affiliation: Department of breast and thyroid surgery, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China. Electronic address: fangdongguo2015@163.com.
authors.forename: Fangdong
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of breast and thyroid surgery, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China.
authors.forename: Hongshen
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chang
authors.affiliation: The Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; IGF-1R; miR-30a; p53R273H