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

• Published in: International journal of molecular sciences Vol. 19; no. 9; p. 2806
• Main Authors: Yang, Chin-An, Li, Ju-Pi, Yen, Ju-Chen, Lai, I-Lu, Ho, Yu-Chen, Chen, Yu-Chia, Lan, Joung-Liang, Chang, Jan-Gowth
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18.09.2018; MDPI
• Subjects: Adult; Aged; Arthritis; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - pathology; Autoimmune diseases; C/EBPβ; Cancer; Cell activation; Cell cycle; Cell Cycle Checkpoints; Cell Differentiation; Cells, Cultured; Chromatin; Costimulator; CXCL10 protein; Cytokines; Dendritic cells; Deoxyribonucleic acid; Differentiation (biology); DNA; Down-Regulation; Female; Gene expression; Hospitals; Humans; Immunoprecipitation; Inflammation; Inflammation - genetics; Inflammation - pathology; Interleukin 10; Leukocytes (mononuclear); Lipopolysaccharides; long noncoding RNA; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - cytology; Macrophages - metabolism; Macrophages - pathology; Male; Middle Aged; monocyte differentiation; Monocytes; Monocytes - cytology; Monocytes - metabolism; Monocytes - pathology; Monocytic leukemia; Neoplasm Proteins - genetics; NTT; Pathogenesis; PBOV1; Peripheral blood mononuclear cells; Proteins; Rheumatoid arthritis; RNA, Long Noncoding - genetics; Transcription factors; Up-Regulation; China; Taiwan; C/EBPβ; long noncoding RNA; monocyte differentiation; rheumatoid arthritis; PBOV1; NTT
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19092806

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 ( ) in monocyte functions. Knockdown and chromatin immunoprecipitation (ChIP) assays in THP-1 cells (human monocytic leukemia cell line) revealed that is regulated by the monocyte key transcription factor C/EBPβ and that it binds to the promoter of nearby gene via hnRNP-U. Overexpression of in THP-1 cells resulted in cell cycle G1 arrest, differentiation into macrophages, a marked increase in and mRNA levels, and upregulation of the costimulatory molecules. In contrast to the downregulated observed in lipopolysaccharide (LPS)-treated THP-1 cells, the 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 expression levels were associated with a trend of higher disease activity DAS28 scores. In conclusion, our study suggests that the lncRNA is a regulator of inflammation in monocytes, and its activation participates in monocyte/macrophage differentiation and the pathogenesis of RA.