miR-125a regulates HAS1 and inhibits the proliferation, invasion and metastasis by targeting STAT3 in non-small cell lung cancer cells
miR-125a regulates HAS1 and inhibits the proliferation, invasion and metastasis by targeting STAT3 in non-small cell lung cancer cells
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DOI：
10.1002/jcb.29586
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发表时间：
2020-01-13
影响因子：
4
通讯作者：
Yang, Zhenzhou
中科院分区：
文献类型：
--
作者：
Huang, Hu;Huang, Jingyu;Yang, Zhenzhou
据相关报道，microRNA-125 a（miR-125 a）与多种癌症的发生、发展和预后有关。然而，其在非小细胞肺癌（NSCLC）中的作用及机制尚待进一步探讨。本研究旨在探讨miR-125 a在NSCLC中的作用及其机制。首先，通过实时定量聚合酶链反应（RT-qPCR）测定，与邻近正常组织相比，miR-125 a在非小细胞肺癌组织中明显下调。STAT 3和HAS 1的表达则相反。此外，miR-125 a在4种人NSCLC细胞系中在A549中表达最高。其次，功能研究表明miR-125 a抑制NSCLC细胞的增殖、侵袭、迁移、转移，促进细胞凋亡，但对细胞周期无明显影响。接着，基于双荧光素酶报告基因测定的预测和确认，结果表明miR-125 a的靶是STAT 3。RT-qPCR和Western blot分析显示，miR-125 a过表达在信使RNA和蛋白水平上显著抑制STAT 3表达。最后，通过PROMO数据库分析和染色质免疫沉淀实验验证了HAS 1启动子区与STAT 3的结合，表明STAT 3与HAS 1启动子区结合。STAT 3过表达在蛋白和mRNA水平上对HAS 1表达有积极影响。此外，HAS 1相关的功能研究表明，HAS 1在体外明显抑制NSCLC细胞的增殖、侵袭和迁移潜力。总的来说，我们的研究结果表明，miR-125 a通过抑制NSCLC中STAT 3表达而降低HAS 1表达来抑制NSCLC细胞的增殖、侵袭和迁移。本研究提示miR-125 a在NSCLC治疗中可能具有潜在的应用价值。
MicroRNA-125a (miR-125a) is related to the occurrence, development, and prognosis of various cancers according to relevant reports. However, its function role and mechanism in non-small cell lung cancer (NSCLC) is yet to be explored. Herein, we investigated the role and preliminary mechanism of miR-125a in NSCLC. First, miR-125a was noticeably downregulated in NSCLC tissues in contrast to adjacent normal tissues through the real-time quantitative polymerase chain reaction (RT-qPCR) assay. The inverted result was observed on the STAT3 and HAS1 expressions. Moreover, miR-125a was expressed at highest level in A549 among four human NSCLC cell lines. Second, functional studies indicated miR-125a restrained proliferation, invasion, migration, metastasis, and advocated apoptosis of NSCLC cells, but had no obvious effect on cell cycle. Next, results indicated that a target of miR-125a was STAT3 on the basis of prediction and confirmation by the dual-luciferase reporter assay. RT-qPCR and Western blot assays displayed that miR-125a overexpression conspicuously constrained STAT3 expression at messenger RNA and protein levels. Finally, the binding between HAS1 promoter region and STAT3 was predicted by PROMO database analysis and verified by chromatin immunoprecipitation assay, suggesting that STAT3 was bound with the HAS1 promoter regions. STAT3 overexpression exerted positive effects on HAS1 expression at protein and mRNA levels. Additionally, HAS1-related functional studies illustrated HAS1 pronouncedly suppressed the proliferative, invasive, and migratory potential of NSCLC cells in vitro. Collectively, our findings demonstrated that miR-125a prohibited the proliferation, invasion, and migration of NSCLC cells by HAS1 expression reduction as a result of inhibiting STAT3 expression in NSCLC. This study indicated that miR-125a might be of potential or value for NSCLC treatment.