PMID- 25194984 OWN - NLM STAT- MEDLINE DCOM- 20150728 LR - 20171116 IS - 1638-6183 (Electronic) IS - 0300-9084 (Linking) VI - 106 DP - 2014 Nov TI - MicroRNA-152 modulates the canonical Wnt pathway activation by targeting DNA methyltransferase 1 in arthritic rat model. PG - 149-56 LID - S0300-9084(14)00247-8 [pii] LID - 10.1016/j.biochi.2014.08.016 [doi] AB - Rheumatoid arthritis (RA) is an autoimmune and progressive systemic disease of unknown etiology. Research shows that fibroblast-like synoviocytes (FLS) participate in the cartilage erosion, synovial hyperplasia, inflammatory cytokine secretion and suggests that fibroblast-like synoviocytes (FLS) display a crucial role in RA pathogenesis. Recent studies have suggested the role of the Wnt signaling pathway in the pathogenesis of RA. In previous study, we identified that increased methyl-CpG-binding protein 2 (MeCP2) reduced the secreted frizzled-related protein 4 (SFRP4) expression in FLS in Arthritic rat model and the DNA methyltransferase (DNMT) inhibitor 5-Aza-2'-deoxycytidine (5-azadC) could induce the SFRP4 expression, indicating that DNMT has a key role in the differential expression of SFRP4. MicroRNAs (MiRNAs), which are small non-coding RNAs, are involved in diverse biological functions, regulation of gene expression, pathogenesis of autoimmune disease and carcinogenesis. In light of the directly down-regulation of miR-152 on DNMT1 expression by targeting the 3' untranslated regions of its transcript in nickel sulfide (NiS)-transformed human bronchial epithelial cells, we investigated whether miR-152 is aberrantly expressed and targets DNMT1 in FLS in Arthritic rat model. Our results demonstrated that the expression of miR-152 was specifically down-regulated in Arthritic rat model, whereas up-regulation of miR-152 in FLS resulted in a marked reduction of DNMT1 expression. Further experiments revealed that increased miR-152 indirectly up-regulated the SFRP4 expression, a negative regulator of WNT signaling pathway, by targeting the DNMT1. Moreover, activation of miR-152 expression in FLS could inhibit the canonical Wnt pathway activation and result in a significant decrease of FLS proliferation. MiR-152 and DNA methylation may provide molecular mechanisms for the activation of canonical Wnt pathway in RA. Combination of miR-152 and DNMT1 may be a promising treatment strategy for RA patients in which SFRP4 is inactivated. CI - Copyright (c) 2014 Elsevier B.V. and Societe francaise de biochimie et biologie Moleculaire (SFBBM). All rights reserved. FAU - Miao, Cheng-Gui AU - Miao CG AD - School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Bengbu 233100, China; School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China. FAU - Yang, Ying-Ying AU - Yang YY AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China. FAU - He, Xu AU - He X AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China. FAU - Huang, Cheng AU - Huang C AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China. FAU - Huang, Yan AU - Huang Y AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China. FAU - Qin, Dan AU - Qin D AD - School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Bengbu 233100, China. FAU - Du, Chuan-Lai AU - Du CL AD - School of Food and Drug, Anhui Key Laboratory of Poultry Epidemic Prevention and Surveillance, Anhui Science and Technology University, Bengbu 233100, China. FAU - Li, Jun AU - Li J AD - School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China. Electronic address: lijunamu@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140904 PL - France TA - Biochimie JT - Biochimie JID - 1264604 RN - 0 (MIRN152 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Sfrp4 protein, rat) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.1.1.37 (DNMT1 protein, human) RN - EC 2.1.1.37 (Dnmt1 protein, rat) SB - IM MH - Animals MH - Arthritis, Experimental/*genetics/metabolism MH - Cell Proliferation/genetics MH - Cells, Cultured MH - DNA (Cytosine-5-)-Methyltransferase 1 MH - DNA (Cytosine-5-)-Methyltransferases/*genetics/metabolism MH - Gene Expression Regulation MH - Humans MH - Immunoblotting MH - Male MH - MicroRNAs/*genetics MH - Proto-Oncogene Proteins/genetics/metabolism MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Synovial Membrane/cytology/metabolism MH - Wnt Signaling Pathway/*genetics OTO - NOTNLM OT - Canonical Wnt pathway OT - DNA methyltransferase 1 OT - MicroRNA-152 OT - Rheumatoid arthritis OT - Secreted frizzled-related protein 4 EDAT- 2014/09/10 06:00 MHDA- 2015/07/29 06:00 CRDT- 2014/09/08 06:00 PHST- 2014/03/11 00:00 [received] PHST- 2014/08/22 00:00 [accepted] PHST- 2014/09/08 06:00 [entrez] PHST- 2014/09/10 06:00 [pubmed] PHST- 2015/07/29 06:00 [medline] AID - S0300-9084(14)00247-8 [pii] AID - 10.1016/j.biochi.2014.08.016 [doi] PST - ppublish SO - Biochimie. 2014 Nov;106:149-56. doi: 10.1016/j.biochi.2014.08.016. Epub 2014 Sep 4.