miR-340 Inhibition of Breast Cancer Cell Migration and Invasion Through Targeting of Oncoprotein c-Met
miR-340 Inhibition of Breast Cancer Cell Migration and Invasion Through Targeting of Oncoprotein c-Met
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DOI：
10.1002/cncr.25860
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发表时间：
2011-07-01
期刊：
影响因子：
6.2
通讯作者：
Zhang, Nong
中科院分区：
文献类型：
--
作者：
Wu, Zheng-sheng;Wu, Qiang;Zhang, Nong
背景：不同的microRNA已被证明在人类癌症中具有致癌和肿瘤抑制功能。检测它们的表达可能会导致识别乳腺癌的新标志物。方法：作者检测了miR-340在4种人乳腺癌细胞系中的表达，并重点研究了其在肿瘤细胞生长、迁移和侵袭以及靶基因表达调控中的作用。然后，他们分析了良性和癌性乳腺组织标本中的miR-340表达。研究结果：内源性miR-340表达在更具侵袭性的乳腺癌细胞系中下调，这在乳腺癌组织标本中通过使用定量实时聚合酶链反应得到证实。进一步的研究表明，诱导miR-340表达能够抑制肿瘤细胞的迁移和侵袭，而敲低miR-340表达则诱导乳腺癌细胞的迁移和侵袭。在基因水平上，作者将c-Met确定为通过调节MMP-2和MMP-9表达介导细胞迁移和侵袭的直接miR-340靶标。在离体条件下，miR-340表达的缺失与乳腺癌的淋巴结转移、高肿瘤组织学分级、临床分期和较短的总生存期以及乳腺癌组织标本中c-Met表达的增加相关。结论：miR-340可能在乳腺癌进展中发挥重要作用，提示miR-340应进一步评估为乳腺癌转移和预后的新生物标志物，并可能成为治疗靶点。Cancer 2011;117：2842-52. (C)2077美国癌症协会
BACKGROUND: Different microRNAs have been shown to have oncogenic and tumor-suppressive functions in human cancers. Detection of their expression may lead to identifying novel markers for breast cancer. METHODS: The authors detected miR-340 expression in 4 human breast cell lines and then focused on its role in regulation of tumor cell growth, migration, and invasion and target gene expression. They then analyzed miR-340 expression in benign and cancerous breast tissue specimens. RESULTS: Endogenous miR-340 expression was down-regulated in the more aggressive breast cancer cell lines, which was confirmed in breast cancer tissue specimens by using quantitative real-time polymerase chain reaction. Further studies showed that induction of miR-340 expression was able to suppress tumor cell migration and invasion, whereas knockdown of miR-340 expression induced breast cancer cell migration and invasion. At the gene level, the authors identified c-Met as a direct miR-340 target to mediate cell migration and invasion through regulation of MMP-2 and MMP-9 expression. Ex vivo, loss of miR-340 expression was associated with lymph node metastasis, high tumor histological grade, clinical stage, and shorter overall survival of breast cancer as well as increased c-Met expression in breast cancer tissue specimens. CONCLUSIONS: miR-340 may play an important role in breast cancer progression, suggesting that miR-340 should be further evaluated as a novel biomarker for breast cancer metastasis and prognosis, and potentially a therapeutic target. Cancer 2011;117:2842-52. (C) 2077 American Cancer Society.