MiR-122 modulates type I interferon expression through blocking suppressor of cytokine signaling 1.
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.
Department of Microbiology, Harbin Medical University, Harbin 150081, China. liaimeiandamy@126.com
Aimei
A
Li
Wuqi
W
Song
Jun
J
Qian
Yujun
Y
Li
Junming
J
He
Qingmeng
Q
Zhang
Wenhui
W
Li
Aixia
A
Zhai
Wenping
W
Kao
Yunlong
Y
Hu
Hui
H
Li
Jing
J
Wu
Hong
H
Ling
Zhaohua
Z
Zhong
Fengmin
F
Zhang
D001483:Base Sequence; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007370:Interferon Type I / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000172:deficiency* / Q000235:genetics*
D007370:Interferon Type I; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins