title: CIP2A expression is associated with synovial hyperplasia and invasive function of fibroblast-like synoviocytes in rheumatoid arthritis.
abstract: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance (P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression (rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS (P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target.
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors.forename: Jaejoon
authors.initials: J
authors.lastname: Lee
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Hwang
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Oh
authors.forename: Hyungjin
authors.initials: H
authors.lastname: Kim
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Bae
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.forename: Jungho
authors.initials: J
authors.lastname: Han
authors.forename: Joong Kyong
authors.initials: JK
authors.lastname: Ahn
authors.forename: Hoon-Suk
authors.initials: HS
authors.lastname: Cha
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Koh
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D001324:Autoantigens / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha