title: microRNA-126 targeting PIK3R2 promotes rheumatoid arthritis synovial fibro-blasts proliferation and resistance to apoptosis by regulating PI3K/AKT pathway.
abstract: OBJECTIVE
  The purpose of our study was to elucidate the impact of microRNA-126 (miR-126) targeting PIK3R2 gene on cell proliferation and apoptosis of rheumatoid arthritis synovial fibro-blasts (RASFs) by regulating PI3K/AKT signal pathway.
  
  
  METHODS
  The synovial tissue samples of this study were from 55 RA patients undergoing joint replacement and 27 healthy people undergoing joint repair due to trauma. The target genes of miR-126 were collected by the TargetScan and PIK3R2 as the direct target gene of miR-126 was confirmed by dual-luciferase reporter assay system. Our experiment had five groups including the blank control, miR-126 mimic, miR-126 mimic control, miR-126 inhibitor and miR-126 inhibitor control groups. Additionally, real-time quantitative polymerase chain reaction (RT-qPCR), Western-Blot, cell counting kit (CCK-8) and flow cytometry were carried out in this study.
  
  
  RESULTS
  Compared with healthy individuals, the RA patients had increased miR-126, but decreased PIK3R2 mRNA expressions in the synovial tissues. Pearson correlation analysis indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (all P<0.05). When compared with the blank group respectively, the miR-126 mimic group had raising cell proportions in S and G2/M phases with reduced rate of cell apoptosis, while the miR-126 inhibitor group had raising cell proportions in G0/G1 and G2/M phases with increased rate of cell apoptosis (all P<0.05). Besides, compared with the blank control group, the miR-126 mimic group had declined expression of PIK3R2 protein with ascended expression of PI3K and p-AKT (all P<0.05), while the miR-126 inhibitor group had increased expression of PIK3R2 protein with decreased expression of PI3K and p-AKT (all P<0.05).
  
  
  CONCLUSIONS
  Our study demonstrated that down-regulation of miR-126 may indirectly inhibit PI3K/AKT signaling pathway to disrupt the imbalance between growth and death of RASFs by targeting PIK3R2, which may be clinically helpful to find therapeutic strategies directed toward miR-126 function for RA patients.
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pathology, Changzhou Second People's Hospital, Changzhou 213003, PR China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Rui-Na
authors.initials: RN
authors.lastname: Kong
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Lian-Mei
authors.initials: LM
authors.lastname: Ji
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: He
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: zhaodongbao1112@163.com.
authors.forename: Dong-Bao
authors.initials: DB
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D055815:Young Adult
chemical_list: C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; C560566:phosphoinositol-3 kinase regulatory subunit 2, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Apoptosis; PI3K/AKT signaling pathway; PIK3R2; Proliferation; Rheumatoid arthritis; Synovial fibro-blasts; microRNA-126