MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis.
MicroRNA-152-mediated dysregulation of hepatic transferrin receptor 1 in liver carcinogenesis.
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DOI：
10.18632/oncotarget.6004
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发表时间：
2016-01-12
期刊：
影响因子：
--
通讯作者：
Pogribny IP
中科院分区：
文献类型：
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作者：
Kindrat I;Tryndyak V;de Conti A;Shpyleva S;Mudalige TK;Kobets T;Erstenyuk AM;Beland FA;Pogribny IP
转铁蛋白受体1（TFRC）的过度表达在肝细胞癌（HCC）中观察到，然而，缺乏关于这种失调的机制的结论性信息。在目前的研究中，我们证明了一个显着增加的TFRC mRNA和蛋白质的水平在癌前肝脏从相关的实验模型的人肝癌和人肝癌细胞。此外，使用TCGA数据库，我们证明了TFRC在人HCC组织样品中的过表达，并且与非肿瘤肝组织相比，microRNA-152（miR-152）的水平显著降低。结果表明，人HCC细胞和人HCC组织样品中TFRC水平的增加可能部分归因于由miR-152的下调介导的转录后机制。这通过人HCC细胞中TFRC水平和miR-152表达之间的强负相关性得到证明（r =-0.99，p = 4. 7 × 10−9），并通过体外实验证实，用miR-152转染人HCC细胞系可有效抑制TFRC表达。这表明TFRC的miR-152特异性靶向可以提供用于治疗HCC的选择性抗癌治疗方法。
Over-expression of transferrin receptor 1 (TFRC) is observed in hepatocellular carcinoma (HCC); however, there is a lack of conclusive information regarding the mechanisms of this dysregulation. In the present study, we demonstrated a significant increase in the levels of TFRC mRNA and protein in preneoplastic livers from relevant experimental models of human hepatocarcinogenesis and in human HCC cells. Additionally, using the TCGA database, we demonstrated an over-expression of TFRC in human HCC tissue samples and a markedly decreased level of microRNA-152 (miR-152) when compared to non-tumor liver tissue. The results indicated that the increase in levels of TFRC in human HCC cells and human HCC tissue samples may be attributed, in part, to a post-transcriptional mechanism mediated by a down-regulation of miR-152. This was evidenced by a strong inverse correlation between the level of TFRC and the expression of miR-152 in human HCC cells (r = −0.99, p = 4. 7 × 10−9), and was confirmed by in vitro experiments showing that transfection of human HCC cell lines with miR-152 effectively suppressed TFRC expression. This suggests that miR-152-specific targeting of TFRC may provide a selective anticancer therapeutic approach for the treatment of HCC.