title: Targeting HER3 with miR-450b-3p suppresses breast cancer cells proliferation.
abstract: In breast cancer cells, heterodimerization of HER2 and HER3 plays important and dominant roles in the functionality and transformation of HER-mediated pathways, in particular the PI3K/Akt survival pathway. HER3 was considered as a major signaling hub in HER2-amplified cancers. Inhibition of HER3 expression may therefore represent a rational therapeutic approach to breast cancers where HER2/HER3-mediated signaling plays a role in tumorigenesis and progression. miRNAs exerts important roles in regulating gene expressions by binding to and repressing target mRNAs. Here we reported that miRNA-450b-3p inhibits HER3 expression by directly targeting 3' UTR of HER3 mRNA and represses the downstream signal transductions of HER family. Overexpression of miRNA-450b-3p in SKBR3 cells inhibits cells clonogenic potential and enhances their sensitivity to trastuzumab, a monoclonal antibody that binds to the HER2 receptor, or doxorubicin through repressing proliferative signal pathways mediated by HER3/HER2/PI3K/AKT. Furthermore, we found that breast cancer patients with tumors that demonstrating upregulated HER3 (> 2-fold) and downregulated miR-450b-3p (> 2-fold) expressions compared with the paired adjacent non-tumorous tissues showed significantly poorer overall survival (P<0.05). Our study identified miRNA-450b-3p as a new tumor repressor and also provided some evidences suggesting that downregulation of miR-450b-3p expression with concurrent overexpression of HER3 may serve as a prognostic biomarker for poor overall survival in breast cancer patients.
authors.affiliation: Department of Oncology; The Affiliated Jiangyin Hospital of Southeast University Medical College; Wuxi, Jiangsu, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Hematology; the First People's Hospital of Yunnan Province; Kunming, Yunnan, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Oncology; The Affiliated Jiangyin Hospital of Southeast University Medical College; Wuxi, Jiangsu, PR China.
authors.forename: Sha
authors.initials: S
authors.lastname: Sha
authors.affiliation: Department of Oncology; The Affiliated Jiangyin Hospital of Southeast University Medical College; Wuxi, Jiangsu, PR China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Oncology; The Affiliated Jiangyin Hospital of Southeast University Medical College; Wuxi, Jiangsu, PR China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Mao
authors.affiliation: Department of Oncology; The Affiliated Jiangyin Hospital of Southeast University Medical College; Wuxi, Jiangsu, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D064593:Heterografts; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D020413:3' Untranslated Regions; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C000589024:MIRN450 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D004317:Doxorubicin; D019869:Phosphatidylinositol 3-Kinases; D020893:Receptor, ErbB-3; D051058:Oncogene Protein v-akt; D000068878:Trastuzumab
keywords: HER3; breast cancer; miRNA-450b-3p