RRC ID 57767
Author Yu C, Shi D, Li Z, Wan G, Shi X.
Title Long noncoding RNA CHRF exacerbates IL-6-induced inflammatory damages by downregulating microRNA-146a in ATDC5 cells.
Journal J Cell Physiol
Abstract Osteoarthritis (OA) is a frequent chronic musculoskeletal disorder which lacks applicably effective therapeutic strategy. In this study, we attempted to investigate whether long noncoding RNA (lncRNA) cardiac hypertrophy-related factor (CHRF) participated in mediating interleukin-6 (IL-6)-induced in vitro inflammatory damages as well as the regulatory mechanisms. ATDC5 cells were stimulated with IL-6, and then cellular damages were evaluated on the basis of cell viability by CCK-8, apoptotic cells by observation with flow cytometry, apoptosis-associated proteins by western blot analysis, and accumulation of inflammatory factors by quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot analysis. Then, effects of lncRNA CHRF on IL-6-treated cells were evaluated. We further explored the downstream factor of lncRNA CHRF and demonstrated whether lncRNA CHRF functioned through the downstream factor. Afterwards, crucial signaling cascades were anatomized. We found that IL-6 reduced cell viability, elevated apoptosis, induced upregulation of inflammatory factors, as well as upregulated lncRNA CHRF and down-regulated miR-146a expression. Then, we found lncRNA CHRF overexpression aggravated IL-6-induced alterations, and lncRNA CHRF knockdown showed the opposite effects. Furthermore, miR-146a was identified to be negatively regulated by lncRNA CHRF, and its overexpression abrogated the roles of lncRNA CHRF in IL-6-treated cells. IL-6-induced the accumulation of IκBα, p65, JAK1, and STAT3 at phosphorylated level was further facilitated by lncRNA CHRF whereas repressed by miR-146a. In conclusion, lncRNA CHRF aggravated the IL-6-induced inflammatory damages in ATDC5 cells. We further outlined a possible mechanism that through downregulating miR-146a, lncRNA CHRF evoked the activation of NF-κB and JAK1/STAT3 signaling cascades.
Volume 234(12)
Pages 21851-21859
Published 2019-12-1
DOI 10.1002/jcp.28749
PMID 31026064
MeSH Cardiomegaly / drug therapy Cardiomegaly / metabolism Chondrocytes / drug effects Chondrocytes / metabolism Humans Interleukin-6 / metabolism Interleukin-6 / pharmacology* MicroRNAs / drug effects MicroRNAs / genetics* Osteoarthritis / drug therapy* Osteoarthritis / genetics RNA, Long Noncoding / genetics RNA, Long Noncoding / pharmacology*
IF 4.522
Times Cited 2
Human and Animal Cells ATDC5(RCB0565)