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
Guoping DingLiping Cao

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...Continue Reading

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