title: Epigenetic silencing of ITGA2 by MiR-373 promotes cell migration in breast cancer.
abstract: The loss of ITGA2 plays an important role in cancer metastasis in several solid cancers. However, the molecular mechanism of ITGA2 loss in primary cancers remains unclear. In this study, we found that a lower ITGA2 protein level was observed in breast cancers compared to adjacent non-cancerous breast tissues. Interestingly, the reduction degree of ITGA2 at the protein level was far more than that at the mRNA level. We further showed that the translation of ITGA2 mRNA was directly inhibited by miR-373 through binding to ITGA2-3'UTR. Silencing of ITGA2 detached cell-cell interactions, induced the deploymerization of stress fiber F-actin and stimulated cancer cell migration, similar to the effect of miR-373 over-expression. The co-expression of ITGA2, not ITGA2-3'UTR, could abrogate miR-373-induced cancer cell migration because that the expression of ITGA2-3'UTR was inhibited by co-transfected miR-373. ITGA2 protein level was inversely associated with miR-373 level in breast cancers (r = -0.663, P<0.001). 73.33% of breast cancer patients with high miR-373 and low ITGA2 expression exhibited the lymph node-positive metastases. Together, our results show that epigenetic silencing of ITGA2 by miR-373 stimulates breast cancer migration, and miR-373high/ITGA2low may be as a prognosis biomarker for breast cancer patients.
authors.affiliation: Institutes of Life and Health Engineering, Jinan University, Guangzhou, China; Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ding
authors.affiliation: Institutes of Life and Health Engineering, Jinan University, Guangzhou, China; Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Fan
authors.affiliation: Institutes of Life and Health Engineering, Jinan University, Guangzhou, China; Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institutes of Life and Health Engineering, Jinan University, Guangzhou, China; Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China.
authors.forename: Jin-Zhou
authors.initials: JZ
authors.lastname: Huang
authors.affiliation: Institutes of Life and Health Engineering, Jinan University, Guangzhou, China; Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China.
authors.forename: Song-Hui
authors.initials: SH
authors.lastname: Xu
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Geng
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, China.
authors.forename: De
authors.initials: D
authors.lastname: Chen
authors.affiliation: Institutes of Life and Health Engineering, Jinan University, Guangzhou, China; Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China; Biomedicine Research Center and Department of Surgery, The Third Affiliated Hospital of Guangzhou Medicine University, Guangzhou, China; Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Guangzhou, China.
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Yan
mesh_terms: D020413:3' Untranslated Regions; D000199:Actins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D017930:Genes, Reporter; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; C056564:ITGA2B protein, human; D039421:Integrin alpha2; C527114:MIRN373 microRNA, human; D035683:MicroRNAs; D008156:Luciferases