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微小RNA-1在食管鳞状细胞癌中的表达下调与临床晚期相关,其过表达可抑制细胞迁移和侵袭。

Downregulation of microRNA-1 in esophageal squamous cell carcinoma correlates with an advanced clinical stage and its overexpression inhibits cell migration and invasion.

作者信息

Yao Li, Zhang Yi, Zhu Qiao, Li Xinyi, Zhu Shaojun, Gong Li, Han Xiujuan, Lan Miao, Li Shanqu, Zhang Wei, Li Yanhong

机构信息

Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.

Cell Engineering Research Center, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

出版信息

Int J Mol Med. 2015 Apr;35(4):1033-41. doi: 10.3892/ijmm.2015.2094. Epub 2015 Feb 9.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of most common and fatal forms of cancer worldwide. Recent studies have suggested that an aberrant microRNA (miRNA or miR) expression signature exists in ESCC. In the present study, in order to determine the involvement of miRNA in the development and progression of ESCC, the expression profiles of miRNA in 8 paired ESCC tissues and corresponding normal esophageal tissues were analyzed by miRNA microarray. A total of 43 differentially expressed miRNAs, including 27 downregulated and 16 upregulated miRNAs were found in the ESCC tissue samples. Among these miRNAs, we found that miR-1 was significantly downregulated. Subsequently, the expression of miR-1 was validated in 64 pairs of primary ESCC samples by RT-qPCR. The expression level of miR-1 was found to be frequently decreased, and significantly correlated with tumor invasion and an advanced clinical stage (P = 0.022 and P = 0.028, respectively). In addition, functional assays revealed that miR-1 inhibited cell proliferation, clonogenicity, cell invasion and migration. Bioinformatics analyses identified the major biological processes that were targeted by miR-1. These results suggest that miR-1 has a tumor-suppressive effect on the development and progression of ESCC. The findings of this study may contribute to the further understanding of the functions of miR-1 in ESCC.

摘要

食管鳞状细胞癌(ESCC)是全球最常见且致命的癌症形式之一。最近的研究表明,ESCC中存在异常的微小RNA(miRNA或miR)表达特征。在本研究中,为了确定miRNA在ESCC发生发展中的作用,通过miRNA芯片分析了8对ESCC组织及相应正常食管组织中miRNA的表达谱。在ESCC组织样本中总共发现了43个差异表达的miRNA,其中包括27个下调的和16个上调的miRNA。在这些miRNA中,我们发现miR-1显著下调。随后,通过RT-qPCR在64对原发性ESCC样本中验证了miR-1的表达。发现miR-1的表达水平经常降低,并且与肿瘤侵袭和临床晚期显著相关(分别为P = 0.022和P = 0.028)。此外,功能分析表明miR-1抑制细胞增殖、克隆形成、细胞侵袭和迁移。生物信息学分析确定了miR-1靶向的主要生物学过程。这些结果表明,miR-1对ESCC的发生发展具有肿瘤抑制作用。本研究结果可能有助于进一步了解miR-1在ESCC中的功能。

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