IFN-γ induces the upregulation of RFXAP via inhibition of miR-212-3p in pancreatic cancer cells: A novel mechanism for IFN-γ response

  • Authors:
    • Guoping Ding
    • Liangjing Zhou
    • Tao Shen
    • Liping Cao
  • View Affiliations

  • Published online on: January 12, 2018     https://doi.org/10.3892/ol.2018.7777
  • Pages:3760-3765
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Abstract

Previous studies have demonstrated that pancreatic cancer-derived microRNA (miR)-212-3p can inhibit the expression of regulatory factor X‑associated protein (RFXAP), an important transcription factor for major histocompatibility complex (MHC) class II, and thereby lead to downregulation of MHC class II in dendritic cells. It has also been established that interferon (IFN)‑γ can increase the expression of MHC class II in immune cells. It was therefore hypothesized that IFN‑γ can inhibit miR‑212‑3p expression in pancreatic cancer, leading to the upregulation of RFXAP and MHC class II expression. This may represent a novel molecular mechanism underlying the use of IFN‑γ in immunotherapy. Data from the present study revealed that miR‑212‑3p was inhibited by IFN‑γ in a dose and time‑dependent manner in the pancreatic ductal adenocarcinoma cell line PANC‑1. RFXAP and MHC class II expression were increased following IFN‑γ stimulation. A luciferase assay was performed to validate RFXAP as a target gene of miR‑212‑3p. The expression levels of RFXAP and MHC class II were decreased by miR‑212‑3p mimics and increased by miR‑212‑3p inhibitors. In PANC‑1 cells transfected with miR‑212‑3p mimics, IFN‑γ stimulation could not increase the RFXAP and MHC class II. The results from the present study suggest that IFN‑γ increases RFXAP and MHC class II expression by inhibiting miR‑212‑3p. To the best of our knowledge, this is the first report of this novel molecular mechanism underlying the effects of IFN‑γ on pancreatic cancer, which may aid with the development of immunotherapies for patients with pancreatic cancer.

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March 2018
Volume 15 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

2016 Impact Factor: 1.39
Ranked #68/217 Oncology
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APA
Ding, G., Zhou, L., Shen, T., & Cao, L. (2018). IFN-γ induces the upregulation of RFXAP via inhibition of miR-212-3p in pancreatic cancer cells: A novel mechanism for IFN-γ response. Oncology Letters, 15, 3760-3765. https://doi.org/10.3892/ol.2018.7777
MLA
Ding, G., Zhou, L., Shen, T., Cao, L."IFN-γ induces the upregulation of RFXAP via inhibition of miR-212-3p in pancreatic cancer cells: A novel mechanism for IFN-γ response". Oncology Letters 15.3 (2018): 3760-3765.
Chicago
Ding, G., Zhou, L., Shen, T., Cao, L."IFN-γ induces the upregulation of RFXAP via inhibition of miR-212-3p in pancreatic cancer cells: A novel mechanism for IFN-γ response". Oncology Letters 15, no. 3 (2018): 3760-3765. https://doi.org/10.3892/ol.2018.7777