LncRNA CASC19 accelerates chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis

Abstract

Background Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown. Methods The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay. Results CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression. Conclusions It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment.

MicroRNA152-3p Protects Against Ischemia/Reperfusion-Induced Bbb Destruction Possibly Targeting the MAP3K2/JNK/c-Jun Pathway

“…miR-152 attenuated lncRNA PVT1induced apoptosis via c-MET/PI3K/AKT pathway in osteosarcoma cell [38]. miR-152-3p regulates TCF-4 pathway in OA rats to weaken chondrocyte apoptosis [39]. miR-152-3p overexpression suppressed angiotensin II-induced [40] and hypoxia-induced cardiomyocyte apoptosis in vitro [41].…”

microRNA152-3p protects against ischemia/reperfusion-induced BBB destruction possibly targeting MAP3K2/JNK/c-Jun pathway

“…Recent years, the anti-apoptotic effect of miR-152-3p in injury diseases have received increasing investment. miR-152-3p regulates TCF-4 pathway in OA rats to weaken chondrocyte apoptosis [31]. miR-152-3p overexpression suppressed angiotensin II-induced apoptosis [32].…”

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

“…In addition, cancer susceptibility 2 (CASC2) [ 56 ] and cancer susceptibility 19 (CASC19) [ 57 ] have been demonstrated to exhibit proinflammatory and proapoptotic effects by regulating IL-17 and the miR-152-3p/DDX6 axis, respectively. Furthermore, Zhang et al [ 58 ] found that the levels of ADP ribosylation factor related protein 1 (ARFRP1) and toll like receptor 4 (TLR4) were increased, whereas those of miR-15a-5p were decreased in lipopolysaccharide (LPS)-treated chondrocytes, and that ARFRP1 promoted the expression of inflammatory molecules, such as IL-6 and TNF-α, by regulating the NF-κB pathway.…”