lncRNA NTT/PBOV1 Axis Promotes Monocyte Differentiation and Is Elevated in Rheumatoid Arthritis

International Journal of Molecular Sciences

Yu-Chia Chen¹  Ju-Pi Li²  Joung-Liang Lan²  Yu-Chen Ho²  Chin-An Yang³  Jan-Gowth Chang³  Ju-Chen Yen⁴  I-Lu Lai⁴ 

[1] Center for Precision Medicine, China Medical University Hospital, Taichung 40447, Taiwan;College of Medicine, China Medical University, Taichung 40402, Taiwan;Department of Laboratory Medicine, China Medical University Hospital, Taichung 40447, Taiwan;Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan;

关键词: long noncoding RNA;    NTT;    C/EBPβ;    PBOV1;    monocyte differentiation;    rheumatoid arthritis;   

DOI  :  10.3390/ijms19092806

来源: DOAJ

【 摘 要 】

Monocytes/macrophages are important in orchestrating inflammatory responses. However, knowledge of the long noncoding RNA (lncRNA) regulation of monocytic cell differentiation and diseases remains limited. We aimed to elucidate the role of the 17 kb lncRNA noncoding transcript in T cells (NTT) in monocyte functions. Knockdown and chromatin immunoprecipitation (ChIP) assays in THP-1 cells (human monocytic leukemia cell line) revealed that NTT is regulated by the monocyte key transcription factor C/EBPβ and that it binds to the promoter of nearby gene PBOV1 via hnRNP-U. Overexpression of PBOV1 in THP-1 cells resulted in cell cycle G1 arrest, differentiation into macrophages, a marked increase in IL-10 and CXCL10 mRNA levels, and upregulation of the costimulatory molecules. In contrast to the downregulated NTT observed in lipopolysaccharide (LPS)-treated THP-1 cells, the C/EBPβ/NTT/PBOV1 axis was found to be hyperactivated in peripheral blood mononuclear cells (PBMCs) of first-time diagnosed untreated early rheumatoid arthritis (RA) patients, and their gene expression levels decreased markedly after treatment. Higher initial C/EBPβ/NTT/PBOV1 expression levels were associated with a trend of higher disease activity DAS28 scores. In conclusion, our study suggests that the lncRNA NTT is a regulator of inflammation in monocytes, and its activation participates in monocyte/macrophage differentiation and the pathogenesis of RA.

【 授权许可】

Unknown