title: MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer.
abstract: Tumor recurrence and metastasis result in an unfavorable prognosis for cancer patients. Recent studies have suggested that specific microRNAs (miRNAs) may play important roles in the development of cancer cells. However, prognostic markers and the outcome prediction of the miRNA signature in breast cancer patients have not been comprehensively assessed. The aim of this study was to identify miRNA biomarkers relating to clinicopathological features and outcome of breast cancer. A miRNA microarray analysis was performed on breast tumors of different lymph node metastasis status and with different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify miRNAs showing a significant difference in expression. The functional interaction between the candidate miRNA, miR-30a, and the target gene, Vim, which codes for vimentin, a protein involved in epithelial-mesenchymal transition, was examined using the luciferase reporter assay, western blotting, and migration and invasion assays. The association between the decreased miR-30a levels and breast cancer progression was examined in a survival analysis. miR-30a negatively regulated vimentin expression by binding to the 3'-untranslated region of Vim. Overexpression of miR-30a suppressed the migration and invasiveness phenotypes of breast cancer cell lines. Moreover, reduced tumor expression of miR-30a in breast cancer patients was associated with an unfavorable outcome, including late tumor stage, lymph node metastasis, and worse progression (mortality and recurrence) (p < 0.05). In conclusion, these findings suggest a role for miR-30a in inhibiting breast tumor invasiveness and metastasis. The finding that miR-30a downmodulates vimentin expression might provide a therapeutic target for the treatment of breast cancer.
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan. cwcheng@csmu.edu.tw
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Cheng
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Chia-Wei
authors.initials: CW
authors.lastname: Chang
authors.forename: Hou-Wei
authors.initials: HW
authors.lastname: Chu
authors.forename: Cheng-You
authors.initials: CY
authors.lastname: Chen
authors.forename: Jyh-Cherng
authors.initials: JC
authors.lastname: Yu
authors.forename: Jui-I
authors.initials: JI
authors.lastname: Chao
authors.forename: Huei-Fang
authors.initials: HF
authors.lastname: Liu
authors.forename: Shian-Ling
authors.initials: SL
authors.lastname: Ding
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D011379:Prognosis; D034622:RNA Interference; D014746:Vimentin / Q000235:genetics*; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D014746:Vimentin