MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer.

MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer.
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MiR-661通过直接抑制RB1促进非小细胞肺癌肿瘤侵袭和转移

DOI:
10.1186/s12943-017-0698-4
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发表时间:
2017-07-17
期刊:
影响因子:
37.3
通讯作者:
Ruan J
Ruan J
中科院分区:
医学1区
文献类型:
--
作者:
Liu F;Cai Y;Rong X;Chen J;Zheng D;Chen L;Zhang J;Luo R;Zhao P;Ruan J

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背景microRNA的异常表达与肿瘤的转移有关。miR-661促进乳腺癌和卵巢癌的增殖和侵袭,而抑制胶质瘤的增殖和侵袭。方法采用实时荧光定量PCR方法检测miR-661在非小细胞肺癌(NSCLC)组织和细胞系中的表达。采用创伤愈合、transwell实验和动物模型评价miR-661对NSCLC迁移、侵袭和转移能力的影响。双报告荧光素酶检测和互补实验进行验证RB 1作为一个直接的目标,miR-661参与的进展NSCLC.ResultsmiR-661是上调NSCLC组织相比,配对的相邻组织和相关的总生存期较短。此外,miR-661还能促进NSCLC的增殖、迁移和转移。因此,我们确定RB 1是miR-661的直接靶点,miR-661通过RB 1影响NSCLC的EMT过程和转移。结论miR-661通过RB/E2 F1信号通路和EMT事件促进NSCLC的转移,可能成为NSCLC患者的一个负性预后因子和可能的治疗靶点。
BackgroundAberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation.MethodsExpression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models. Dual reporter luciferase assay and complementary experiments were performed to validate RB1 as a direct target of miR-661 for participation in the progression of NSCLC.ResultsMiR-661 was upregulated in NSCLC tissues as compared to paired adjacent tissues and associated with shorter overall survival. Furthermore, miR-661 promoted proliferation, migration and metastasis of NSCLC. Then, we identified RB1 as a direct target of miR-661 through which miR-661 affected EMT process and metastasis of NSCLC. RB1 interacted with E2F1 and both could mediate EMT process in NSCLC.ConclusionMiR-661 promotes metastasis of NSCLC through RB/E2F1 signaling and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of NSCLC patient.
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