Abstract
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.
Highlights
MicroRNAs are endogenous small noncoding RNAs that regulate cellular gene expression and are functionally linked to tumorigenesis [1]
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
Patients with a high serum IL-6 concentration had significantly shorter survival times than those with a low serum IL-6 concentration. These results indicate that a high serum IL-6 concentration is associated with postoperative recurrence and can be used as a predictor for survival of patients with hepatocellular carcinoma (HCC)
Summary
MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate cellular gene expression and are functionally linked to tumorigenesis [1]. The authors indicated that the reduction of miR-26a expression may be used as an independent predictor of survival for HCC patients. The authors found that the miR-26a reduction in cancerous tissues is accompanied by a concomitant elevation in interleukin (IL)-6 expression [4]. MiR-26a expression has been found to be transcriptionally downregulated by oncogene c-Myc in a variety of human cancers [3,5,6]. Several studies have determined that IL-6 can induce a significant induction of c-Myc expression in cancer cells including human HCC HepG2 cells [7,8,9]. It is reasonable to hypothesize that the miR-26a reduction in HCC is the consequence, at least in part, of elevated IL-6 expression
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