miR-122-SOCS1-JAK2 axis regulates allergic inflammation and allergic inflammation-promoted cellular interactions
- 주제(키워드) allergic inflammation , cellular interaction , miR-122 , SOCS1 , tumor microenvironments
- 등재 SCIE, SCOPUS
- 발행기관 IMPACT JOURNALS LLC
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000147263
- 본문언어 영어
- Published As http://dx.doi.org/10.18632/oncotarget.19149
초록/요약
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-beta 1 (TGF-beta 1) was decreased during allergic inflammation and showed an anti-allergic effect. SOCS1 and JAK2 regulated the production of anti-allergic TGF-beta 1. 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.
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