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

Autor: I-Lu Lai, Joung-Liang Lan, Ju-Chen Yen, Jan-Gowth Chang, Chin-An Yang, Yu-Chia Chen, Ju-Pi Li, Yu-Chen Ho
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
rheumatoid arthritis
Cellular differentiation
Monocytes
Arthritis
Rheumatoid
lcsh:Chemistry
Gene expression
lcsh:QH301-705.5
Cells
Cultured
Spectroscopy
Gene knockdown
Cell Differentiation
General Medicine
Middle Aged
Neoplasm Proteins
Up-Regulation
Computer Science Applications
medicine.anatomical_structure
Monocyte differentiation
C/EBPβ
Monocytic leukemia
Female
RNA
Long Noncoding
Adult
NTT
Down-Regulation
Biology
Peripheral blood mononuclear cell
Article
Catalysis
monocyte differentiation
Inorganic Chemistry
03 medical and health sciences
medicine
Humans
CXCL10
long noncoding RNA
Physical and Theoretical Chemistry
Molecular Biology
Aged
Inflammation
Macrophages
Monocyte
Organic Chemistry
Cell Cycle Checkpoints
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
PBOV1
Zdroj: International Journal of Molecular Sciences, Vol 19, Iss 9, p 2806 (2018)
International Journal of Molecular Sciences
Volume 19
Issue 9
ISSN: 1422-0067
Popis: 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/EBP&beta
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/EBP&beta
/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/EBP&beta
/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.
Databáze: OpenAIRE
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