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微小RNA-1470的过表达促进食管鳞状癌细胞的增殖和迁移,并抑制其衰老。

Overexpression of microRNA-1470 promotes proliferation and migration, and inhibits senescence of esophageal squamous carcinoma cells.

作者信息

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

机构信息

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

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

出版信息

Oncol Lett. 2017 Dec;14(6):7753-7758. doi: 10.3892/ol.2017.7190. Epub 2017 Oct 16.

Abstract

MicroRNA-1470 (miR-1470) is overexpressed in esophageal squamous cell carcinoma (ESCC); however, its role and underlying molecular mechanism remain unknown. The aim of the present study was to explore the tumorigenic role and mechanism of miR-1470 overexpression in ESCC. The expression of miR-1470 in ESCC tissues and cell lines was detected using human miRNA microarrays and the reverse transcription-quantitative polymerase chain reaction, respectively. The effects of miR-1470 on cell proliferation, migration and senescence were determined using a Cell Counting Kit-8 assay, Transwell migration assay and β-galactosidase staining kit. Western blotting was used to analyze the expression levels of genes in the apoptosis signaling pathway. An increased expression level of miR-1470 was observed in ESCC tissues compared with that in paracancerous tissues. Knockdown of miR-1470 significantly suppressed proliferation, and down-regulated the cell cycle regulatory gene cyclin E1. It was also revealed that knockdown of miR-1470 significantly inhibited migration, and decreased the expression levels of matrix metalloproteinase 2 (MMP2), MMP13 and MMP14. Western blotting analysis revealed that knockdown of miR-1470 induced apoptosis by increasing B-cell lymphoma 2 (Bcl-2) expression. The results of the present study suggest that overexpression of miR-1470 in ESCC promotes cancer cell proliferation by accelerating the cell cycle and inhibiting apoptosis, and also enhances cancer cell migration by upregulating MMPs.

摘要

微小RNA-1470(miR-1470)在食管鳞状细胞癌(ESCC)中过表达;然而,其作用及潜在分子机制仍不清楚。本研究的目的是探讨miR-1470过表达在ESCC中的致瘤作用及机制。分别使用人miRNA芯片和逆转录-定量聚合酶链反应检测ESCC组织和细胞系中miR-1470的表达。使用细胞计数试剂盒-8检测、Transwell迁移试验和β-半乳糖苷酶染色试剂盒确定miR-1470对细胞增殖、迁移和衰老的影响。采用蛋白质免疫印迹法分析凋亡信号通路中基因的表达水平。与癌旁组织相比,ESCC组织中miR-1470的表达水平升高。敲低miR-1470可显著抑制增殖,并下调细胞周期调节基因细胞周期蛋白E1。还发现敲低miR-1470可显著抑制迁移,并降低基质金属蛋白酶2(MMP2)、MMP13和MMP14的表达水平。蛋白质免疫印迹分析显示,敲低miR-1470可通过增加B细胞淋巴瘤2(Bcl-2)表达诱导细胞凋亡。本研究结果表明,ESCC中miR-1470的过表达通过加速细胞周期和抑制凋亡促进癌细胞增殖,并通过上调基质金属蛋白酶增强癌细胞迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f71/5755030/27518c30bd0d/ol-14-06-7753-g00.jpg

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