IL-6 upregulation contributes to the reduction of miR-26a expression in hepatocellular carcinoma cells.
IL-6 upregulation contributes to the reduction of miR-26a expression in hepatocellular carcinoma cells.
复制标题
DOI：
10.1590/s0100-879x2012007500155
复制
发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Rao Z
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhang B;Zhang A;Li X;Liu J;Zhao J;Zhao Y;Gao J;Fang D;Rao Z
最近的一项研究表明，miR-26a在肝细胞癌组织中下调，这种下调是一个独立的生存预测因素。有趣的是，同一项研究还报告了miR-26a下调会导致IL-6表达的伴随上调。由于在多种肿瘤中发现miR-26a的表达受癌基因c-Myc的转录下调，而c-Myc的表达受IL-6的刺激而上调，我们推测IL-6在肝细胞癌中参与了miR-26a的表达下调。采用双抗体夹心法检测血清IL-6水平，定量RT-PCR法检测miR-26a水平。对30例肝细胞癌手术切除患者的资料表明，血清IL-6水平可作为预测肝细胞癌患者生存期长达5年的指标(Log-ranch检验，P<；0.05)。我们观察到血清IL-6浓度与癌组织中miR-26a表达呈负相关(Pearson相关检验，r=-0.651，P<0.01)。此外，通过体外实验，我们发现IL-6刺激可通过激活c-Myc抑制miR-26a的表达，而在正常肝细胞中，IL-6对miR-26a的表达无明显影响。以上结果提示，肝细胞癌miR-26a表达下调可能是由于IL-6表达上调所致。
A recent study showed that miR-26a is downregulated in hepatocellular carcinoma tissues and that this downregulation is an independent predictor of survival. Interestingly, the same study also reported that miR-26a downregulation causes a concomitant elevation of IL-6 expression. Because miR-26a expression was found to be transcriptionally downregulated by oncogene c-Myc in various cancers, and the expression of c-Myc was increased by IL-6 stimulation, we hypothesized that IL-6 contributes to reduction of miR-26a in hepatocellular carcinoma. Serum IL-6 was measured by ELISA and miR-26a was detected by qRT-PCR. The data of 30 patients with hepatocellular carcinoma who had undergone surgical tumor resection revealed that serum IL-6 could be considered to be a predictor of survival up to 5 years for hepatocellular carcinoma patients (log-rank test, P < 0.05). We observed that the serum IL-6 concentration was inversely correlated with miR-26a expression in cancerous tissues (Pearson correlation test, r = -0.651, P < 0.01). Furthermore, by in vitro experiments with HepG2 cells, we showed that IL-6 stimulation can lead to miR-26a suppression via c-Myc activation, whereas in normal hepatocyte LO2 cells incubation with IL-6 had no significant effect on miR-26a expression. Taken together, these results indicate that miR-26a reduction in hepatocellular carcinoma might be due to IL-6 upregulation.