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Long Non-Coding RNA AL928768.3 Promotes Rheumatoid Arthritis Fibroblast-Like Synoviocytes Proliferation, Invasion and Inflammation, While Inhibits Apoptosis Via Activating Lymphotoxin Beta Mediated NF-κB Signaling Pathway

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Abstract

Our previous study using RNA sequencing and reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation identified a long non-coding RNA (lnc), lnc-AL928768.3, correlating with risk and disease activity of rheumatoid arthritis (RA), then the present study was conducted to further investigate the interaction of lnc-AL928768.3 with lymphotoxin beta (LTB) and their impact on proliferation, migration, invasion, and inflammation in RA-fibroblast-like synoviocytes (RA-FLS). Human RA-FLS was obtained and transfected with lnc-AL928768.3 overexpression, negative control overexpression, lnc-AL928768.3 short hairpin RNA (shRNA) and negative control shRNA plasmids. Then cell functions and inflammatory cytokine expressions were detected. Afterward, rescue experiments were conducted via transfecting lnc-AL928768.3 shRNA with or without LTB overexpression plasmids in RA-FLS. Lnc-AL928768.3 enhanced proliferation and invasion, inhibited apoptosis, while had little impact on migration in RA-FLS. In addition, lnc-AL928768.3 positively modulated interleukin-1β (IL-1β), IL-6 and IL-8 expressions in RA-FLS supernatant; moreover, it also positively regulated LTB mRNA expression, LTB protein expression, p-NF-κB protein expression, and p-IKB-α protein expression in RA-FLS. Furthermore, following experiment showed that lnc-AL928768.3 positively regulated LTB expression while LTB did not impact on lnc-AL928768.3 expression in RA-FLS. Furthermore, in rescue experiments, LTB overexpression curtailed the effect of lnc-AL928768.3 knock-down on regulating proliferation, invasion, apoptosis and inflammatory cytokine expressions in RA-FLS. Lnc-AL928768.3 promotes proliferation, invasion, and inflammation while inhibits apoptosis of RA-FLS via activating LTB mediated NF-κB signaling.

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Availability of Data And Materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

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Funding

This study was supported by Natural Science Foundation of Zhejiang Province, China (Grant/Award Number: LY20H100002), Medical Science Research Foundation of Zhejiang Province, China (Grant/Award Number: 2020KY634) and Wenzhou Science and Technology Foundation (Grant/Award Number: Y2020922).

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  1. Li Sun and Lingzhen Hu contributed equally.

Authors and Affiliations

  1. Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Kidney Disease Prevention and Control Technology National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University; Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, Zhejiang Province, China

    Li Sun & Jianghua Chen

  2. Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

    Lingzhen Hu, Peirong Chen, Yongji Li & Jianxin Tu

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  1. Li Sun
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Contributions

JC contributed to the conception and design of the study. LS and LH contributed to the data acquisition. PC and YL contributed to the analysis and interpretation of data. JT contributed to drafting/revising of article. All authors read and approved the final manuscript.

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Correspondence to Jianghua Chen.

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Sun, L., Hu, L., Chen, P. et al. Long Non-Coding RNA AL928768.3 Promotes Rheumatoid Arthritis Fibroblast-Like Synoviocytes Proliferation, Invasion and Inflammation, While Inhibits Apoptosis Via Activating Lymphotoxin Beta Mediated NF-κB Signaling Pathway. Inflammation 47, 543–556 (2024). https://doi.org/10.1007/s10753-023-01927-x

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