Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDH Inhibits Cell Growth and Induces Apoptosis by Regulating the PTEN/AKT Pathway in Hepatocellular Carcinoma.
Lentiviral-Mediated Short Hairpin RNA Knockdown of MTDH Inhibits Cell Growth and Induces Apoptosis by Regulating the PTEN/AKT Pathway in Hepatocellular Carcinoma.
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慢病毒介导的短发夹 RNA 敲低 MTDH 通过调节肝细胞癌中的 PTEN/AKT 通路抑制细胞生长并诱导细胞凋亡
DOI：
10.3390/ijms160819419
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发表时间：
2015-08-17
影响因子：
5.6
通讯作者：
Liu CA
中科院分区：
文献类型：
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作者：
Li WF;Ou Q;Dai H;Liu CA
癌基因的激活和抑癌基因的缺失被认为在人肝细胞癌（HCC）的发病机制中起关键作用。Metaherin（MTDH），也称为星形胶质细胞升高基因-1（AEG-1），在多种癌症中经常扩增，但MTDH在HCC中生长和凋亡方面的作用尚未研究。在本研究中，我们首先分析了MTDH在HCC样本中的表达。我们发现MTDH蛋白水平在大多数HCC癌组织中高于其匹配的邻近非肿瘤组织。此外，MTDH mRNA在HCC组织中也高于其匹配的邻近非肿瘤组织。使用小干扰RNA敲低内源性MTDH进一步表明MTDH的缺乏抑制HCC细胞的生长并引起细胞凋亡。敲低MTDH可促进肝癌细胞中PTEN和p53的表达，并抑制AKT磷酸化。敲低MTDH也抑制体内肿瘤生长。这些结果表明，MTDH蛋白在大多数肝癌组织中的表达水平高于非肿瘤组织，并且MTDH的敲低通过激活PTEN抑制肝癌细胞的生长并诱导其凋亡。因此，MTDH可能是一种有效的肝癌靶向治疗基因。
The activation of oncogenes and the loss of tumor suppressor genes are believed to play critical roles in the pathogenesis of human hepatocellular carcinoma (HCC). Metaherin (MTDH), also called astrocyte elevated gene-1 (AEG-1), is frequently amplified in a variety of cancers, but the roles of MTDH with regard to growth and apoptosis in HCC have not yet been studied. In the present study, we first analyzed the expression of MTDH in HCC samples. We found that MTDH protein levels are higher in most HCC cancerous tissues compared with their matched adjacent non-tumor tissues. Additionally, the MTDH mRNA was also higher in HCC tissues compared to their matched adjacent non-tumor tissues. Knockdown of the endogenous MTDH using small interfering RNA further showed that deficiency of MTDH suppressed cell growth and caused apoptosis in HCC cells. Knockdown MTDH promoted PTEN and p53 expression in HCC cells and inhibited AKT phosphorylation. Knockdown MTDH also inhibited tumor growth in vivo. All these results indicated that MTDH protein levels in most HCC tissues are higher than non-tumor tissues, and knockdown of MTDH inhibited growth and induced apoptosis in HCC cells through the activation of PTEN. Therefore, MTDH might be an effective targeted therapy gene for HCC.