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微小RNA-27a-3p通过靶向Yes相关蛋白1调控口腔鳞状细胞癌细胞的上皮-间质转化

MicroRNA-27a-3p regulates epithelial to mesenchymal transition via targeting YAP1 in oral squamous cell carcinoma cells.

作者信息

Zeng Guang, Xun Wenxing, Wei Kewen, Yang Yongjin, Shen Huan

机构信息

Department of Plastic and Burn Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.

Department of Stomatology, The General Hospital of the Second Artillery Corps of Chinese PLA, Beijing 100088, P.R. China.

出版信息

Oncol Rep. 2016 Sep;36(3):1475-82. doi: 10.3892/or.2016.4916. Epub 2016 Jul 7.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs frequently dysregulated in human malignancies. Here, we profiled isolated cells from freshly resected tumors from oral squamous cell carcinoma (OSCC) patients and OSCC cell lines using a SYBR Green-based qPCR miRNA array to identify the expression change of the miRNAs. Based on the microarray data and clincopathological factor analysis of 50 OSCC patients related to these miRNAs, miR-27a-3p was selected as a putative miRNA which might play important role in OSCC progression. By bioinformatics analysis and dual-luciferase reporter assay, we found that YAP1 (Yes-associated protein-1) was a direct target gene of miR-27a-3p. Intriguingly, increased expression of miR-27a-3p could significantly decrease the expression level of YAP1 as well as several epithelial to mesenchymal transition (EMT)-related molecules in OSCC cell lines, including Twist and Snail. Then, follow-up studies revealed that miR-27a-3p expression was able to downregulate the EMT-related molecules effectively, which might be involved in the regulation of Sox2 via the YAP1-OCT4-Sox2 signaling axis. In summary, this study found that miR-27a-3p could inhibit the YAP1 directly by post-transcriptionally silencing and potentially suppress EMT process, suggesting that miR‑27a-3p might play pivotal roles in effectively manipulating the invasion and metastasis in oral squamous cell carcinoma cells through the EMT inhibition.

摘要

微小RNA(miRNA)是一类小的非编码RNA,在人类恶性肿瘤中经常发生失调。在此,我们使用基于SYBR Green的qPCR miRNA芯片对口腔鳞状细胞癌(OSCC)患者新鲜切除肿瘤及OSCC细胞系中的分离细胞进行分析,以鉴定miRNA的表达变化。基于50例与这些miRNA相关的OSCC患者的芯片数据和临床病理因素分析,miR-27a-3p被选为一种可能在OSCC进展中起重要作用的miRNA。通过生物信息学分析和双荧光素酶报告基因检测,我们发现YAP1(Yes相关蛋白-1)是miR-27a-3p的直接靶基因。有趣的是,miR-27a-3p表达增加可显著降低OSCC细胞系中YAP1以及几种上皮-间质转化(EMT)相关分子(包括Twist和Snail)的表达水平。随后的研究表明,miR-27a-3p表达能够有效下调EMT相关分子,这可能通过YAP1-OCT4-Sox2信号轴参与对Sox2的调控。总之,本研究发现miR-27a-3p可通过转录后沉默直接抑制YAP1,并可能抑制EMT过程,提示miR-27a-3p可能通过抑制EMT在有效调控口腔鳞状细胞癌细胞的侵袭和转移中发挥关键作用。

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