Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma
Caveolin-1 mediates tumor cell migration and invasion and its regulation by miR-133a in head and neck squamous cell carcinoma
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DOI：
10.3892/ijo_00000840
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发表时间：
2011-01-01
影响因子：
5.2
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
--
作者：
Nohata, Nijiro;Hanazawa, Toyoyuki;Seki, Naohiko
MicroRNAs(MiRNAs)是由大约22个核苷酸组成的非编码小RNA，在人类癌症中可以作为癌基因或肿瘤抑制因子发挥作用。在许多类型的癌症中miRNA miR-133a的下调，以及由于过度表达而减少细胞的增殖、迁移和侵袭，表明miR-133a是一种肿瘤抑制因子。在本研究中，对过表达miR-133a的HNSCC细胞进行全基因组基因表达分析，结果表明多功能支架蛋白小窝蛋白1(CAV1)表达下调，这一结果得到了实时定量聚合酶链式反应和Western印迹分析的证实。荧光素酶报告实验表明miR-133a直接与CAV1mRNA结合。转染si-CAV1的HNSCC细胞的癌细胞迁移和侵袭受到明显抑制。因此，CAV1在HNSCC中起癌基因的作用。肿瘤抑制基因miRNAs及其靶基因的发现将为深入研究HNSCC的致癌机制提供新的思路。
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides that can function as oncogenes or tumor suppressors in human cancer. Downregulation of the miRNA miR-133a in many type of cancers, and a reduction of cell proliferation, migration, and invasion upon over-expression, suggests that miR-133a is a tumor suppressor. In this study, genome-wide gene expression analysis of HNSCC cells that over-express miR-133a showed that caveolin-1 (CAV1), a multifunctional scaffolding protein, is down-regulated, a result that was confirmed by real-time PCR and Western blot analysis. A luciferase reporter assay revealed that miR-133a is directly bound to CAV1 mRNA. Cancer cell migration and invasion were significantly inhibited in HNSCC cells transfected with si-CAV1. Therefore, CAV1 functions as an oncogene in HNSCC. The identification of tumor suppressive miRNAs and their target genes could provide new insights into potential mechanism of HNSCC carcinogenesis.