MicroRNA-181c Inhibits Interleukin-6-mediated Beta Cell Apoptosis by Targeting TNF-α Expression

• Published in: Molecules (Basel, Switzerland) Switzerland), 2019-04, Vol.24 (7), p.1410
• Main Authors: Oh, Yoon Sin, Bae, Gong Deuk, Park, Eun-Young, Jun, Hee-Sook
• Format: Article
• Language: English
• Subjects: Annexin V; Antibodies; Apoptosis; beta cell apoptosis; Beta cells; Cell viability; Cytokines; Cytotoxicity; Diabetes; Gene expression; Inflammation; Insulin resistance; Interleukin 6; Metabolic disorders; microRNA-181c; MicroRNAs; miRNA; Obesity; Proteins; Stat3 protein; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24071410

We have previously reported that long-term treatment of beta cells with interleukin-6 (IL-6) is pro-apoptotic. However, little is known about the regulatory mechanisms that are involved. Therefore, we investigated pro-apoptotic changes in mRNA expression in beta cells in response to IL-6 treatment. We analyzed a microarray with RNA from INS-1 beta cells treated with IL-6, and found that TNF-α mRNA was significantly upregulated. Inhibition of TNF-α expression by neutralizing antibodies significantly decreased annexin V staining in cells compared with those treated with a control antibody. We identified three microRNAs that were differentially expressed in INS-1 cells incubated with IL-6. In particular, miR-181c was significantly downregulated in IL-6-treated cells compared with control cells and the decrease of miR-181c was attenuated by STAT-3 signaling inhibition. TNF-α mRNA was a direct target of miR-181c and upregulation of miR-181c by mimics, inhibited IL-6-induced increase in TNF-α mRNA expression. Consequently, reduction of TNF-α mRNA caused by miR-181c mimics enhanced cell viability in IL-6 treated INS-1 cells. These results demonstrated that miR-181c regulation of TNF-α expression plays a role in IL-6-induced beta cell apoptosis.