Open Access

MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells

  • Authors:
    • Yihe Yan
    • Zhihai Liang
    • Qiang Du
    • Muqing Yang
    • David A. Geller
  • View Affiliations

  • Published online on: June 9, 2016     https://doi.org/10.3892/or.2016.4864
  • Pages: 633-640
  • Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Interferon regulatory factor-1 (IRF-1) is a tumor-suppressor gene induced by interferon-γ (IFNγ) and plays an important role in the cell death of hepatocellular carcinoma (HCC). HCC tumors evade death in part by downregulating IRF-1 expression, yet the molecular mechanisms accounting for IRF-1 suppression in HCC have not yet been characterized. Previous studies have shown that microRNA-23a (miR-23a) can suppress apoptosis by targeting IRF-1. Therefore, we hypothesized that miR-23a promotes HCC growth by downregulating IRF-1. For the in vivo studies, 7 cases of resected HCC and adjacent liver samples were analyzed. For the in vitro studies, IRF-1 mRNA and protein were examined in HepG2 and Huh-7 HCC cells after IFNγ stimulation by real-time PCR and western blotting, respectively. To determine the role of miR-23a in regulating IRF-1, HepG2 cells were transfected with an miR-23a mimic or inhibitor, and IRF-1 expression was examined. Binding of miR-23a was assessed by cloning the 528-bp human IRF-1 3'-untranslated region (3'UTR) into luciferase reporter plasmid pMIR-IRF-1-3'UTR. The results showed that IRF-1 mRNA expression was downregulated in the human HCC tumor tissues compared to that in the adjacent background liver tissues. IFNγ-induced IRF-1 protein was less in the HepG2 tumor cells compared to that in the primary human hepatocytes. miR-23a expression was inversely correlated with IRF-1, and addition of the miR-23a inhibitor increased basal IRF-1 mRNA and protein. Likewise, the miR-23a mimic downregulated IFNγ-induced IRF-1 protein expression, while the miR-23a inhibitor increased IRF-1. Furthermore, the miR-23a mimic repressed IRF-1-3'UTR reporter activity, while the miR-23a inhibitor increased the reporter activity. These results demonstrated that IRF-1 expression is downregulated in human HCC tumors compared to that noted in the background liver. miR-23a downregulates the expression of IRF-1 in HCC cells, and the IRF-1 3'UTR has an miR‑23a binding site that binds miR-23a and decreases reporter activity. These findings suggest that the targeting of IRF-1 by miR-23a may be the molecular basis for IRF-1 downregulation in HCC and provide new insight into the regulation of HCC by miRNAs.
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August-2016
Volume 36 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yan Y, Liang Z, Du Q, Yang M and Geller DA: MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells. Oncol Rep 36: 633-640, 2016.
APA
Yan, Y., Liang, Z., Du, Q., Yang, M., & Geller, D.A. (2016). MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells. Oncology Reports, 36, 633-640. https://doi.org/10.3892/or.2016.4864
MLA
Yan, Y., Liang, Z., Du, Q., Yang, M., Geller, D. A."MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells". Oncology Reports 36.2 (2016): 633-640.
Chicago
Yan, Y., Liang, Z., Du, Q., Yang, M., Geller, D. A."MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells". Oncology Reports 36, no. 2 (2016): 633-640. https://doi.org/10.3892/or.2016.4864