Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea.
Rheumatol Int. 2012 Jul;32(7):2023-30. doi: 10.1007/s00296-011-1927-6. Epub 2011 Apr 9.
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.
致癌性蛋白磷酸酶 2A 抑制剂（CIP2A）是一种新发现的癌蛋白，可导致癌细胞增殖。我们旨在研究成纤维细胞样滑膜细胞（FLS）中 CIP2A 的表达及其与滑膜炎的组织病理学分级以及 FLS 在类风湿关节炎（RA）中的侵袭功能的关系。使用 Western blot 分析测量了 8 例 RA FLS 和 8 例 OA FLS 中的 CIP2A 蛋白表达。使用实时 PCR 测量了 19 例 RA FLS 和 7 例 OA FLS 中的 CIP2A mRNA 表达。两名独立病理学家对 RA FLS 匹配的滑膜组织的滑膜炎评分进行了半定量测量。使用 CIP2A 小干扰 RNA（siRNA）或对照载体处理 RA FLS 进行体外细胞侵袭实验。Western blot 分析表明，与 OA FLS 相比，CIP2A 在 RA FLS 中更频繁地过度表达。RA FLS 中的 CIP2A mRNA 表达高于 OA FLS，但无统计学意义（P = 0.076）。在 RA 中，总滑膜炎评分与 FLS CIP2A mRNA 表达呈强相关（rs = 0.849，P = 0.043）。TNF-α 处理诱导对照 FLS 的侵袭功能明显增强（P = 0.0021），但在 CIP2A siRNA 处理的 FLS 中未观察到明显作用。我们的数据表明，CIP2A 的表达与 RA 中滑膜炎的组织病理学评分和 FLS 的侵袭功能密切相关。这些结果表明 CIP2A 可能在 RA 的破坏性过程中起关键作用，并需要进一步研究 CIP2A 作为治疗靶标。
