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Inflammation

, Volume 41, Issue 5, pp 1661–1670 | Cite as

Sam68 Promotes Invasion, Migration, and Proliferation of Fibroblast-like Synoviocytes by Enhancing the NF-κB/P65 Pathway in Rheumatoid Arthritis

  • Weiwei Sun
  • Rongqin Qin
  • Rui Wang
  • Dazhi Ding
  • Zhaohui Yu
  • Yuxi Liu
  • Ruilong Hong
  • Zhen Cheng
  • Youhua Wang
ORIGINAL ARTICLE

Abstract

Src-associated substrate during mitosis of 68 KDa (Sam68), also known as KH domain containing, RNA binding, signal transduction associated 1 (KHDRBS1), is the prototypic member of the signal transduction activator of RNA (STAR) family of RNA-binding proteins. Previous studies have indicated that Sam68 regulates nuclear transcription factor kappa B (NF-κB) to mediate inflammation. In this study, we analyzed the effect and possible mechanisms of Sam68 in rheumatoid arthritis (RA). By western blot analysis and immunohistochemistry, we found that the expression of Sam68 in synovial tissue of RA patients was increased compared with the control group. Immunoflourescent staining demonstrated that Sam68 co-localized with fibroblast-like synoviocytes (FLS) of RA patients. Additionally, the expression of Sam68 in FLS was increased by tumor necrosis factor (TNF)-α stimulation, in a time-dependent manner. Upon TNF-α treatment, Sam68 translocated from the cytoplasm to the nucleus where it interacted with the p65 subunit of NF-κB, as examined by immunoprecipitation and immunofluorescent staining assay. Furthermore, inhibiting the expression of Sam68 by siRNA significantly suppressed the TNF-α-induced expression of interleukin (IL)-6, and matrix metalloproteinase (MMP)-1, reduced the proliferation, migration, and invasion, and markedly decreased the phosphorylation of P65 and IκBα in FLS. Collectively, our findings suggested that Sam68 contributed to the production of inflammatory cytokines, proliferation, migration, and invasion of RA FLS through the NF-κB P65 signal transduction pathway and underscored the importance of Sam68 in the inflammation process of RA.

KEY WORDS

Sam68 rheumatoid arthritis (RA) fibroblast-like synoviocytes tumor necrosis factor-α (TNF-α) P65 

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OrthopedicsAffiliated Hospital of Nantong UniversityJiangsuChina
  2. 2.North Sichuan Medical CollegeNanchongChina

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