微小RNA-450a在肝细胞癌中靶向DNA甲基转移酶3a。
microRNA-450a targets DNA methyltransferase 3a in hepatocellular carcinoma.
作者信息
Weng Zhihong, Wang Dongdong, Zhao Wenyue, Song Mengqi, You Faping, Yang Lian, Chen Libo
机构信息
Department of Hepatology and Infectious Disease;
出版信息
Exp Ther Med. 2011 Sep;2(5):951-955. doi: 10.3892/etm.2011.288. Epub 2011 Jun 17.
Abstract
microRNAs (miRNAs) have been proven to play key regulatory roles in hepatocarcinogenesis. In the present study, the possible role of microRNA-450a (miR-450a) in hepatocarcinogenesis was investigated. Our study revealed that miR-450a was significantly down-regulated in hepatocellular carcinoma (HCC) tissues compared with that in normal liver (NL) and para-tumorous (PT) tissues, and miR-450a expression in HepG2 cells was significantly lower than that in L02 cells. Both the mRNA and protein levels of the miR-450a potential target gene, DNA methyltransferase 3a (DNMT3a), were obviously higher in HCC compared with levels in the NL and PT tissues. We further identified DNMT3a as the direct target gene for miR-450a, and ectopic miR-450a expression in HepG2 cells caused the down-regulation of DNMT3a and an inhibition of cell proliferation. Taken together, these findings suggest that miR-450a plays an important regulatory role in hepatocarcinogenesis through inhibition of DNMT3a expression, and miR-450a may be a potential target for the treatment of HCC.
摘要
微小RNA（miRNA）已被证明在肝癌发生过程中发挥关键调控作用。在本研究中，我们调查了微小RNA - 450a（miR - 450a）在肝癌发生中的可能作用。我们的研究显示，与正常肝脏（NL）组织和癌旁（PT）组织相比，miR - 450a在肝细胞癌（HCC）组织中显著下调，并且在HepG2细胞中的miR - 450a表达明显低于L02细胞。miR - 450a潜在靶基因DNA甲基转移酶3a（DNMT3a）的mRNA和蛋白质水平在HCC中均明显高于NL和PT组织中的水平。我们进一步确定DNMT3a是miR - 450a的直接靶基因，并且在HepG2细胞中异位表达miR - 450a导致DNMT3a下调并抑制细胞增殖。综上所述，这些发现表明miR - 450a通过抑制DNMT3a表达在肝癌发生中发挥重要调控作用，并且miR - 450a可能是治疗HCC的潜在靶点。
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本文引用的文献
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