MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer
MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer
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DOI：
10.1007/s10549-012-2034-4
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发表时间：
2012-08-01
影响因子：
3.8
通讯作者：
Shen, Chen-Yang
中科院分区：
文献类型：
--
作者：
Cheng, Chun-Wen;Wang, Hsiao-Wei;Shen, Chen-Yang
肿瘤的复发和转移导致癌症患者的预后不良。最近的研究表明，特定的microRNAs（miRNAs）可能在癌细胞的发展中发挥重要作用。然而，乳腺癌患者的预后标志物和miRNA标签的结果预测尚未得到全面评估。本研究的目的是鉴定与乳腺癌临床病理特征和预后相关的miRNA生物标志物。对不同淋巴结转移状态和具有不同进展特征（由细胞周期蛋白D1和β-连环蛋白基因的过表达指示）的乳腺肿瘤进行miRNA微阵列分析，以鉴定显示表达显著差异的miRNA。利用荧光素酶报告基因分析、蛋白质印迹以及迁移和侵袭分析来检查候选miRNA miR-30 a与靶基因Vim之间的功能性相互作用，所述靶基因编码波形蛋白（一种参与上皮-间质转化的蛋白质）。在生存分析中检查了降低的miR-30 a水平与乳腺癌进展之间的关联。miR-30 a通过与Vim的3 '非翻译区结合负调控波形蛋白的表达。过表达miR-30 a可抑制乳腺癌细胞系的迁移和侵袭表型。此外，乳腺癌患者中miR-30 a的肿瘤表达降低与不利的结果相关，包括晚期肿瘤分期、淋巴结转移和更差的进展（死亡率和复发）（p < 0.05）。总之，这些发现表明miR-30 a在抑制乳腺肿瘤侵袭和转移方面发挥作用。miR-30 a下调波形蛋白表达的发现可能为乳腺癌的治疗提供一个治疗靶点。
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 beta-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.