title: Mycophenolic acid upregulates miR-142-3P/5P and miR-146a in lupus CD4+T cells.
abstract: BACKGROUND
  Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), is a noncompetitive inhibitor of inosine monophosphate dehydrogenase, and is now widely used for the treatment of systemic lupus erythematosus (SLE). Dysregulated expression of microRNA has been reported to be associated with the pathogenesis of SLE. However, it is unexplored whether altering microRNA expression in SLE patients is one of the therapeutic effects of MPA.
  
  
  OBJECTIVE
  This study thus aims to investigate the effect of MPA on microRNAs expression in lupus CD4(+)T cells and its underlying mechanisms.
  
  
  RESULTS
  According to our microarray data, 101 upregulated microRNAs and 77 downregulated microRNAs were identified in MPA-treated lupus CD4(+)T cells. Among these microRNAs, miR-142-3p/5p and miR-146a expression was found to be significantly increased in MPA-treated lupus CD4(+)T cells compared to untreated controls. Furthermore, we observed that MPA-treated CD4(+)T cells from patients with SLE showed enriched levels of H4 acetylation in the putative miRNA-142 regulatory region and enhanced levels of H3 acetylation in the putative miRNA-146a regulatory region compared to untreated cells.
  
  
  CONCLUSIONS
  Data from this study suggest that MPA activates miR-142 and miR-146a expression through histone modification at the promoter region, which may partially explain the pharmacological mechanisms of MPA for SLE.
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
authors: Q
authors: Q
authors: Tang
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
authors: Y
authors: Y
authors: Yang
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
authors: M
authors: M
authors: Zhao
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
authors: G
authors: G
authors: Liang
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
authors: H
authors: H
authors: Wu
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
authors: Q
authors: Q
authors: Liu
authors: Changsha Blood Center, Changsha, Hunan, China.
authors: Y
authors: Y
authors: Xie
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.
authors: D
authors: D
authors: Li
authors: Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
authors: Y
authors: Y
authors: Dai
authors: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors: S
authors: S
authors: Yung
authors: Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors: T M
authors: TM
authors: Chan
authors: Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China qianlu5860@gmail.com.
authors: Q
authors: Q
authors: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009173:Mycophenolic Acid / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: C555159:MIRN142 microRNA, human; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D023201:CD40 Ligand; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; D009173:Mycophenolic Acid
keywords: CD4+T cells; Systemic lupus erythematosus; microRNAs; mycophenolic acid