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hsa-miR-34c 通过靶向 c-Met 抑制人喉癌细胞的生长和侵袭。

Hsa-miR-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-Met.

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Taizhou People's Hospital, Taizhou 225300, Jiangsu, P.R. China.

出版信息

Int J Mol Med. 2010 Apr;25(4):565-71. doi: 10.3892/ijmm_00000378.

DOI:10.3892/ijmm_00000378
PMID:20198305
Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively modulate gene expression at the post-transcriptional level. A growing number of studies has shown that more and more miRNAs are aberrantly expressed and involved in the pathogenesis of several types of cancers. Here, we report that the down-regulated hsa-miR-34c was also involved in oncogenesis of laryngeal carcinoma. Our studies indicated that hsa-miR-34c functioned as a tumor suppressor which inhibited growth and invasion of human laryngeal carcinoma cells. Furthermore, in our study, an inverse relationship between the expression of hsa-miR-34c and c-Met was identified in 10 paired fresh samples from tumor tissues and adjacent normal tissues. Infection of hsa-miR-34c mediated by lentivirus suppressed the expression of c-Met directly. In addition, introduction of c-Met cDNA lacking 3'-UTR largely abrogated hsa-miR-34c-induced cell growth and invasion inhibition. These findings suggest aberrantly down-regulated hsa-miR-34c is a critical factor that contributes to malignancy in human laryngeal carcinoma by a mechanism involving targeting of c-Met.

摘要

微小 RNA(miRNAs)是一类小的非编码 RNA 分子,可在转录后水平负调控基因表达。越来越多的研究表明,越来越多的 miRNAs 表达异常,并参与多种类型癌症的发病机制。在这里,我们报告下调的 hsa-miR-34c 也参与喉癌的发生。我们的研究表明,hsa-miR-34c 作为一种肿瘤抑制因子,抑制人喉癌细胞的生长和侵袭。此外,在我们的研究中,在 10 对来自肿瘤组织和相邻正常组织的新鲜样本中鉴定到 hsa-miR-34c 和 c-Met 的表达呈负相关。通过慢病毒介导的 hsa-miR-34c 感染可直接抑制 c-Met 的表达。此外,引入缺乏 3'-UTR 的 c-Met cDNA 可显著消除 hsa-miR-34c 诱导的细胞生长和侵袭抑制。这些发现表明,异常下调的 hsa-miR-34c 是导致人喉癌细胞恶性转化的关键因素,其机制涉及到对 c-Met 的靶向作用。

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