A novel long non-coding RNA, lnc-RNU12, influences the T-cell cycle via c-JUN and CCNL2 in rheumatoid arthritis

Author:

Mo Xing-Bo12,Sun Yang-Hua12,Wu Long-Fei12,He Pei12,Cao Rong-Rong12,Lu Xin12,Zhang Yong-Hong2,Deng Fei-Yan12,Lei Shu-Feng12ORCID

Affiliation:

1. Center for Genetic Epidemiology and Genomics, School of Public Health, Medical College of Soochow University , Suzhou, Jiangsu, P. R. China

2. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University , Suzhou, Jiangsu, P. R. China

Abstract

Abstract Objectives Long non-coding RNAs (lncRNAs) play important roles in RA pathogenesis. However, specific lncRNAs that regulate gene expression in RA pathogenesis are poorly known. This study was undertaken to characterize a novel lncRNA (lnc-RNU12) that has a lower-than-normal expression level in RA patients. Methods We performed initial genome-wide lncRNA microarray screening in peripheral blood mononuclear cells from 28 RA cases and 18 controls. Multiple methods were used to validate the detected associations between lncRNAs and RA. Furthermore, we identified the source and characteristics of the highlighted lncRNAs, detected the target genes, and determined the functional effect on immune cells through lncRNA knock-down in Jurkat T cell lines. Results lnc-RNU12 was downregulated in peripheral blood mononuclear cells and T cell subtypes of RA patients and was genetically associated with RA risk. lnc-RNU12 mediates the effect of microbiome alterations on RA risk. Activation of T cells caused low expression of lnc-RNU12. Knock-down of lnc-RNU12 in Jurkat T cells caused cell cycle S-phase arrest and altered the expression of protein-coding genes related to the cell cycle and apoptosis (e.g. c-JUN, CCNL2, CDK6, MYC, RNF40, PKM, VPS35, DNAJB6 and FLCN). Finally, c-JUN and CCNL2 were identified as target genes of lnc-RNU12 at the mRNA and protein expression levels. RNA-binding protein immunoprecipitation assays verified the interaction between lnc-RNU12 and the two proteins (c-Jun and cyclin L2) in Jurkat cells. Conclusions Our study suggested that lnc-RNU12 was involved in the pathogenesis of RA by influencing the T cell cycle by targeting c-JUN and CCNL2.

Funder

National Natural Science Foundation of China

Science and Technology Project of Suzhou

QingLan Research Project of Jiangsu Province

Priority Academic Program Development of Jiangsu Higher Education Institutions

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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