MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin
MicroRNA-30a suppresses breast tumor growth and metastasis by targeting metadherin
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MicroRNA-30a 通过靶向metadherin抑制乳腺肿瘤生长和转移
DOI：
10.1038/onc.2013.286
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发表时间：
2014-06-12
期刊：
影响因子：
8
通讯作者：
Yang, Q.
中科院分区：
文献类型：
--
作者：
Zhang, N.;Wang, X.;Yang, Q.
越来越多的数据表明，microRNAs作为癌基因或抑癌基因参与了癌症过程。在这里，我们建立了miR-30a作为乳腺癌发生和转移过程中的肿瘤抑制基因。在乳腺癌细胞系中异位表达miR-30a可抑制细胞生长和体外转移。一直以来，异种移植小鼠模型也揭示了miR-30a对肿瘤生长和远端肺转移的抑制作用。通过双荧光素酶报告基因分析，我们发现miR-30a能与金属粘附素基因的3‘-非翻译区结合，从而对金属粘附素基因发挥抑制作用。此外，我们还发现，沉默mtdh可以概括miR-30a过表达的作用，而过表达mtdh可以部分消除miR-30a介导的抑制作用。有意义的是，miR-30a在乳腺癌组织中的表达水平显著低于配对的正常组织。进一步的评估证实miR-30a与乳腺癌患者的淋巴转移和肺转移呈负相关。综上所述，我们的研究结果表明miR-30a通过直接靶向亚甲基二氢叶酸脱氢酶抑制乳腺癌的增殖和转移，miR-30a可以作为乳腺癌的预后标志。MiR-30a的操作可能为乳腺癌的治疗提供一种有前途的治疗策略。
Accumulating data have shown the involvement of microRNAs in cancerous processes as either oncogenes or tumor suppressor genes. Here, we established miR-30a as a tumor suppressor gene in breast cancer development and metastasis. Ectopic expression of miR-30a in breast cancer cell lines resulted in the suppression of cell growth and metastasis in vitro. Consistently, the xenograft mouse model also unveiled the suppressive effects of miR-30a on tumor growth and distal pulmonary metastasis. With dual luciferase reporter assay, we revealed that miR-30a could bind to the 3′-untranslated region of metadherin (MTDH) gene, thus exerting inhibitory effect on MTDH. Furthermore, we demonstrated that silence of MTDH could recapitulate the effects of miR-30a overexpression, while overexpression of MTDH could partially abrogate miR-30a-mediated suppression. Of significance, expression level of miR-30a was found to be significantly lower in primary breast cancer tissues than in the paired normal tissues. Further evaluation verified that miR-30a was negatively correlated with the extent of lymph node and lung metastasis in patients with breast cancer. Taken together, our findings indicated miR-30a inhibits breast cancer proliferation and metastasis by directly targeting MTDH, and miR-30a can serve as a prognostic marker for breast cancer. Manipulation of miR-30a may provide a promising therapeutic strategy for breast cancer treatment.