LncRNA NONHSAT042241 inhibits rheumatoid synovial proliferation, inflammation and aggression via inactivating WNT/β-catenin signaling pathway
Yehua Jin,
Cen Chang,
Xinpeng Zhou,
Runrun Zhang,
Ping Jiang,
Kai Wei,
Linshuai Xu,
Yiming Shi,
Guizhen Yang,
Xinliang Lv,
Yuejuan Zheng,
Dongyi He
Affiliations
Yehua Jin
Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Cen Chang
Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Xinpeng Zhou
Department of Rheumatology, Shandong Province Hospital of Traditional Chinese Medicine, Jinan, China
Runrun Zhang
Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
Ping Jiang
Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Kai Wei
Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Linshuai Xu
Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Yiming Shi
Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China
Guizhen Yang
Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xinliang Lv
Department of Rheumatology, Traditional Chinese Medicine Hospital of Inner Mongolia Autonomous Region, Hohhot, Inner Mongolia Autonomous Region, China
Yuejuan Zheng
Center for Traditional Chinese Medicine and Immunology Research, School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Dongyi He
Department of Rheumatology, Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
Objective This study aims to explore the effect of NONHSAT042241 on the function of rheumatoid arthritis -fibroblast-like synoviocyte (RA-FLS) and the underlying mechanisms.Methods RA-FLS was treated with NONHSAT042241 overexpression and NONHSAT042241 knockdown lentiviruses. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, Transwell assay, western-blot, ELISA, and qRT-PCR were used to measure the changes of cell proliferation, apoptosis, invasion, secretion of inflammatory cytokines and matrix metalloproteinases (MMPs). Fluorescent in situ hybridization (FISH) assay, RNA pull-down assay, mass spectrometry (MS) and RNA immunoprecipitation (RIP) were used to find the target proteins that bond to NONHSAT042241, and western-blot was used to detect the expression of related proteins of Wnt/β-catenin signaling pathway.Results Overexpression of NONHSAT042241 inhibited the proliferation of RA-FLS (p < 0.05), invasion, secretion of pro-inflammatory factors (IL-1and IL-6) and MMPs (MMP-1 and MMP-3) (p < 0.05), and elevated the level of pro-apoptotic factors (Bax and cleaved caspase3), while NONHSAT042241 knockdown had the opposite effect. NONHSAT042241 can directly bind to hnRNP D, and down-regulated the expression of β-catenin (p < 0.05), p-GSK-3β (p < 0.05), Cyclin D1 (p < 0.05), PCNA (p < 0.05), and thus reduced the cell proliferation.Conclusion NONHSAT042241 may inhibit FLS-mediated rheumatoid synovial proliferation, inflammation and aggression. The underlying mechanisms may be that NONHSAT042241 inhibits the activity of Wnt/β-catenin signaling.
