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Original article
miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD
  1. Chong He1,
  2. Yan Shi1,
  3. Ruijin Wu1,
  4. Mingming Sun1,
  5. Leilei Fang1,
  6. Wei Wu1,2,
  7. Changqin Liu1,
  8. Maochun Tang1,
  9. Zhong Li1,
  10. Ping Wang3,
  11. Yingzi Cong2,4,
  12. Zhanju Liu1
  1. 1Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
  2. 2Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA
  3. 3Central Laboratory for Medical Research, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
  4. 4Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA
  1. Correspondence to Dr Zhanju Liu, Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China; liuzhanju88{at}


Objective MicroRNA (miR)-301a is known to be involved in the tumourigenesis and pathogenesis of several autoimmune diseases, but it remains unclear whether miR-301a is associated with the pathogenesis of IBD.

Methods miR-301a expression was assessed in peripheral blood mononuclear cells (PBMC) and inflamed mucosa of patients with IBD by quantitative real-time-PCR. Peripheral blood CD4+ T cells were transduced with lentivirus-encoding pre-miR-301a (LV-miR-301a) or a reverse complementary sequence of miR-301a (LV-anti-miR-301a), and their differentiation and activation were investigated in vitro. Antisense miR-301a was administered into mice during trinitrobenzene sulphonic acid (TNBS)-induced colitis to determine its role in colitis.

Results miR-301a expression was significantly upregulated in PBMC and inflamed mucosa of patients with IBD compared with healthy controls. Stimulation with tumour necrosis factor-α (TNF-α) significantly enhanced miR-301a expression in IBD CD4+ T cells, which was markedly reversed by anti-TNF-α mAb (Infliximab) treatment. Transduction of LV-miR-301a into CD4+ T cells from patients with IBD promoted the Th17 cell differentiation and TNF-α production compared with the cells with expression of LV-anti-miR-301a. SNIP1 as a functional target of miR-301a was reduced in miR-301a expression but increased in LV-anti-miR-301a expression. Knockdown of SNIP1 could enhance Th17 cell differentiation. Furthermore, intracolonical administration of antisense miR-301a in TNBS-induced mouse colitis model significantly decreased numbers of interleukin (IL)-17A+ cells and amounts of pro-inflammatory cytokines (eg, IL-17A, TNF-α) in inflamed colon.

Conclusions Our data reveal a novel mechanism in which the elevated miR-301a in PBMC and inflamed mucosa of IBD promotes Th17 cell differentiation through downregulation of SNIP1. Blockade of miR-301a in vivo may serve as a novel therapeutic approach in the treatment of IBD.


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  • CH, YS and RW share the first authorship.

  • Contributors ZLiu and YC planned and supervised the experimental work and data analyses; CH, YS, RW and MS performed all the experiments; WW, LF, ZLi and PW analysed the data; CL, MT and ZLiu diagnosed the patients and provided clinical information and samples and CH, YC and ZLiu wrote the manuscript. All authors discussed and revised the manuscript.

  • Funding This work is financially supported by grants from the National Natural Science Foundation of China (81270470, 81470822).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Institutional Review Board for Clinical Research of the Shanghai Tenth People's Hospital of Tongji University.

  • Provenance and peer review Not commissioned; externally peer reviewed.