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miR-145-5p通过调控食管鳞状细胞癌中的Sp1/NF-κB信号通路抑制肿瘤细胞迁移、侵袭及上皮-间质转化

miR-145-5p Suppresses Tumor Cell Migration, Invasion and Epithelial to Mesenchymal Transition by Regulating the Sp1/NF-κB Signaling Pathway in Esophageal Squamous Cell Carcinoma.

作者信息

Mei Li-Li, Wang Wen-Jun, Qiu Yun-Tan, Xie Xiu-Feng, Bai Jie, Shi Zhi-Zhou

机构信息

Medical School, Kunming University of Science and Technology, Kunming 650500, China.

State Key Laboratory of Molecular Oncology, Cancer Hospital, CAMS, Beijing 100021, China.

出版信息

Int J Mol Sci. 2017 Aug 23;18(9):1833. doi: 10.3390/ijms18091833.

Abstract

MicroRNAs (miRNAs) play important roles in the progression of human cancer. Although previous reports have shown that miR-145-5p is down-regulated in esophageal squamous cell carcinoma (ESCC), the roles and mechanisms of down-regulation of miR-145-5p in ESCC are still largely unknown. Using microRNA microarray and Gene Expression Omnibus (GEO) datasets, we confirmed that miR-145-5p was down-regulated in ESCC tissues. In vitro assays revealed that ectopic miR-145-5p expression repressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT). miR-145-5p also reduced the expressions of cell cycle genes including cyclin A2 (), cyclin D1 () and cyclin E1 (), the EMT-associated transcription factor Slug, and matrix metalloproteinases (MMPs) including , and . Furthermore, miR-145-5p mimics reduced candidate target gene specificity protein 1 () and nuclear factor κ B () () both in mRNA and protein levels. Knockdown of phenocopied the effects of miR-145-5p overexpression on cell cycle regulators, EMT and the expression of (). Importantly, inhibition of the signaling pathway or knockdown of () phenocopied the effects of miR-145-5p on the migration, invasion and EMT of ESCC cells. In conclusion, our results suggested that miR-145-5p plays tumor-suppressive roles by inhibiting esophageal cancer cell migration, invasion and EMT through regulating the signaling pathway.

摘要

微小RNA(miRNA)在人类癌症进展中发挥着重要作用。尽管先前的报道表明miR-145-5p在食管鳞状细胞癌(ESCC)中表达下调,但其在ESCC中下调的作用和机制仍 largely unknown。利用微小RNA微阵列和基因表达综合数据库(GEO)数据集,我们证实miR-145-5p在ESCC组织中表达下调。体外实验表明,异位表达miR-145-5p可抑制细胞增殖、迁移、侵袭以及上皮-间质转化(EMT)。miR-145-5p还降低了包括细胞周期蛋白A2()、细胞周期蛋白D1()和细胞周期蛋白E1()在内的细胞周期基因的表达,EMT相关转录因子Slug以及包括 、 和 在内的基质金属蛋白酶(MMP)的表达。此外,miR-145-5p模拟物在mRNA和蛋白质水平上均降低了候选靶基因特异性蛋白1()和核因子κB()()的表达。敲低 可模拟miR-145-5p过表达对细胞周期调节因子、EMT以及 ()表达的影响。重要的是,抑制 信号通路或敲低 ()可模拟miR-145-5p对ESCC细胞迁移、侵袭和EMT的影响。总之,我们的结果表明,miR-145-5p通过调节 信号通路抑制食管癌细胞的迁移、侵袭和EMT,从而发挥肿瘤抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a2/5618482/327febe1a5d3/ijms-18-01833-g001.jpg

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