miR-122-SOCS1-JAK2 axis regulates allergic inflammation and allergic inflammation-promoted cellular interactions

Abstract

// Kyeonga Noh 1, * , Misun Kim 1, * , Youngmi Kim 1, * , Hanearl Kim 1 , Hyuna Kim 1 , Jaehwan Byun 1 , Yeongseo Park 1 , Hansoo Lee 2 , Yun Sil Lee 3 , Jongseon Choe 4 , Young Myeong Kim 4 and Dooil Jeoung 1 1 Department of Biochemistry, Kangwon National University, Chunchon 24341, Korea 2 Department of Biological Sciences, Kangwon National University, Chunchon 24341, Korea 3 College of Pharmacy, Ewha Womans University, Seoul 03760, Korea 4 Graduate School of Medicine, Kangwon National University, Chunchon 24341, Korea * These authors have contributed equally to this work Correspondence to: Dooil Jeoung, email: jeoungd@kangwon.ac.kr Keywords: allergic inflammation, cellular interaction, miR-122, SOCS1, tumor microenvironments Received: December 09, 2016     Accepted: June 19, 2017     Published: July 10, 2017 ABSTRACT The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation. TargetScan analysis predicted the binding of miR-122 to the 3′-UTR of SOCS1. miR-122 inhibitor induced in vitro and in vivo allergic features in SOCS1-dependent manner. SOCS1 was necessary for allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells. SOCS1 and miR-122 regulated cellular interactions involving cancer cells, mast cells and macrophages during allergic inflammation. SOCS1 mimetic peptide, D-T-H-F-R-T-F-R-S-H-S-D-Y-R-R-I, inhibited in vitro and in vivo allergic inflammation, allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells, and cellular interactions during allergic inflammation. Janus kinase 2 (JAK2) exhibited binding to SOCS1 mimetic peptide and mediated allergic inflammation. Transforming growth factor- ß1 (TGF-ß1) was decreased during allergic inflammation and showed an anti-allergic effect. SOCS1 and JAK2 regulated the production of anti-allergic TGF-ß1. Taken together, our results show that miR-122-SOCS1 feedback loop can be employed as a target for the development of anti-allergic and anti-cancer drugs.