miR-183 inhibits TGF-beta1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells.
miR-183 inhibits TGF-beta1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells.
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DOI：
10.1186/1471-2407-10-354
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发表时间：
2010-07-06
期刊：
影响因子：
3.8
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Li J;Fu H;Xu C;Tie Y;Xing R;Zhu J;Qin Y;Sun Z;Zheng X
近年来，一些miRNAs被报道与人肝细胞癌的发生发展密切相关。在我们之前的研究中，一组miRNAs在肝癌组织中被发现是异常调节的。然而，这些miRNAs在肝细胞癌中的功能在很大程度上仍不清楚。采用qRT-PCR方法比较miR-183在肝细胞癌组织和癌旁正常肝组织中的表达。该方法用于筛选miR-183的潜在靶基因。进行荧光素酶报告实验以确认靶标关联。最后，检测miR-183对肝癌细胞的功能作用。在分析的25个肝癌样本中，与匹配的非肿瘤肝组织相比，17个样本中microRNA-183显著上调(两倍至367倍)。程序性细胞死亡4(PDCD4)基因被确定为miR-183的靶基因。此外，pDCD4是参与转化生长因子-β-1诱导人肝癌细胞凋亡的促凋亡分子，我们发现mIR-183对转化生长因子-β-1诱导人肝癌细胞的凋亡具有抵抗作用，提示mIR-183可能通过抑制pDCD4的表达而抑制人肝癌细胞的凋亡，在肝癌的发生发展中可能起重要作用。
In recent years, some miRNAs have been reported to be connected closely with the development of human hepatocellular carcinoma. In our previous studies, a set of miRNAs were revealed to be dysregulated in HCC tissues. However, the functions of these miRNAs in HCC remain largely undefined. The expression profiles of miR-183 were compared between HCC tissues and adjacent normal liver tissues using qRT-PCR method. This method was used to screen the potential target genes of miR-183. A luciferase reporter assay was conducted to confirm target association. Finally, the functional effect of miR-183 in hepatoma cells was examined. Among the 25 HCC samples analyzed, microRNA-183 was significantly up-regulated (twofold to 367-fold) in 17 samples compared with the matching nontumoral liver tissues. Programmed cell death 4 (PDCD4) was identified as the target gene of miR-183. Moreover, PDCD4 is a proapoptotic molecule involved in TGF-β1-induced apoptosis in human HCC cells, we found that miR-183 transfectants were resistant to apoptosis induced by TGF-β1. We conclude that miR-183 can inhibit apoptosis in human HCC cells by repressing the PDCD4 expression, and miR-183 may play an important role in HCC development.