MiR-122 modulates type I interferon expression through blocking suppressor of cytokine signaling 1

• Published in: The international journal of biochemistry & cell biology 2013-04, Vol.45 (4), p.858-865
• Main Authors: Li, Aimei, Song, Wuqi, Qian, Jun, Li, Yujun, He, Junming, Zhang, Qingmeng, Li, Wenhui, Zhai, Aixia, Kao, Wenping, Hu, Yunlong, Li, Hui, Wu, Jing, Ling, Hong, Zhong, Zhaohua, Zhang, Fengmin
• Format: Article
• Language: English
• Subjects: Base Sequence; Cell Line, Tumor; cytokines; Down-Regulation - genetics; fluorescence; Gene Expression Regulation - genetics; green fluorescent protein; Hepatitis C virus; Hepatocytes; Hepatocytes - metabolism; Humans; Immunity, Innate - genetics; Interferon Type I - genetics; interferons; liver; messenger RNA; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-122; MiRNA; mutation; patients; plasmids; protein synthesis; RNA, Messenger - genetics; RNA, Messenger - metabolism; screening; signal transduction; Suppressor of cytokine signaling 1; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins - deficiency; Suppressor of Cytokine Signaling Proteins - genetics; therapeutics; Type I interferon
• ISSN: 1357-2725; 1878-5875
• DOI: 10.1016/j.biocel.2013.01.008

[Display omitted] ► SOCS1 is a target of miR-122 in hepatocytes. ► MiR-122 targets the nt359–nt375 region of SOCS1 mRNA and regulates its expression. ► MiR-122 could modulate type I IFN expression in hepatocytes. ► MiR-122 might be a critical factor for the efficiency of the IFN therapy. MiR-122 is a liver-specific miRNA. Recent studies demonstrated that the interferon (IFN) therapy efficacy is poor in the hepatitis C virus (HCV)-infected patients with lower miR-122 abundance in the livers. The hepatocarcinoma patients also have low miR-122 levels in their livers. We previously found that the IFN expression was reduced when miR-122 was knocked down in human oligodendrocytes. The mechanism is unclear. In this study, the miR-122-abundant cell Huh7 was used to explore the regulatory mechanism of miR-122 on type I IFN expression. We found that miR-122 significantly increased the type I IFN expression in Huh7 cells, while knocking down miR-122 decreased the type I IFN expression. By screening potential miR-122 targets among the negative regulators in IFN signaling pathways, we found that there were putative miR-122 targets in the suppressor of cytokine signaling 1 (SOCS1) mRNA. Over-expressing miR-122 decreased the SOCS1 expression by 50.55% in Huh7 cells, while knocking down miR-122 increased SOCS1 expression by 62.56%. Using a green fluorescence protein (EGFP) fused SOCS1-expressing plasmid, the SOCS1-EGFP fluorescence intensity and protein were lower in miR-122 mimic-treated cells than those in mock-miRNA-treated cells, while miR-122 knockdown significantly increased the SOCS1-EGFP fluorescence intensity and protein expression. Mutations in the nt359–nt375 region abandoned the impact of miR-122 on SOCS1-EGFP expression. Taken together, SOCS1 is a target of miR-122. MiR-122 can regulate the type I IFN expression through modulating the SOCS1 expression.