MicroRNA-205 targets SMAD4 in non-small cell lung cancer and promotes lung cancer cell growth in vitro and in vivo.
MicroRNA-205 targets SMAD4 in non-small cell lung cancer and promotes lung cancer cell growth in vitro and in vivo.
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DOI：
10.18632/oncotarget.10339
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发表时间：
2017-05-09
期刊：
影响因子：
--
通讯作者：
Huang JA
中科院分区：
文献类型：
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作者：
Zeng Y;Zhu J;Shen D;Qin H;Lei Z;Li W;Liu Z;Huang JA
尽管在诊断和治疗方面取得了进展，但非小细胞肺癌（NSCLC）患者的生存率仍然很差;因此，需要提高对疾病机制的理解和新的治疗策略。已经报道了SMAD4的下调和miR-205的表达失调。然而，它们之间的关系仍然不清楚。我们研究了microRNA（miR）-205对NSCLC中SMAD4表达的影响。SMAD4的敲低和过表达分别促进或抑制细胞活力和增殖，并加速或抑制NSCLC细胞的细胞周期。SMAD4的3 ′-非翻译区（3 ′-UTR）被预测为miR-205的靶点。荧光素酶分析证实miR-205直接与SMAD4 3 ′-UTR结合。蛋白和mRNA表达分析证实，miR-205在NSCLC细胞中的过表达抑制SMAD 4 mRNA和蛋白的表达。在人NSCLC组织中，经常观察到miR-205表达增加，并且与SMAD4表达减少呈负相关。miR-205在NSCLC细胞中的异位表达抑制细胞活力和增殖，加速细胞周期，并促进肺癌裸鼠移植瘤的生长。我们的研究表明，miR-205降低SMAD4表达，从而促进NSCLC细胞生长。我们的研究结果强调了靶向miR-205在NSCLC治疗中的治疗潜力。
Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor; therefore, improved understanding of the disease mechanism and novel treatment strategies are needed. Downregulation of SMAD4 and dysregulated expression of miR-205 have been reported. However, the relationship between them remains unclear. We investigated the effect of microRNA (miR)-205 on the expression of SMAD4 in NSCLC. Knockdown and overexpression of SMAD4 promoted or suppressed cellular viability and proliferation, and accelerated or inhibited the cell cycle in NSCLC cells, respectively. The 3′-untranslated region (3′-UTR) of SMAD4 was predicted as a target of miR-205. Luciferase assays validated that miR-205 binds directly to the SMAD4 3′-UTR. Protein and mRNA expression analyses confirmed that miR-205 overexpression in NSCLC cells inhibited the expression of SMAD4 mRNA and protein. In human NSCLC tissues, increased miR-205 expression was observed frequently and was inversely correlated with decreased SMAD4 expression. Ectopic expression of miR-205 in NSCLC cells suppressed cellular viability and proliferation, accelerated the cell cycle, and promoted tumor growth of lung carcinoma xenografts in nude mice. Our study showed that miR-205 decreased SMAD4 expression, thus promoting NSCLC cell growth. Our findings highlighted the therapeutic potential of targeting miR-205 in NSCLC treatment.