circFADS2 protects LPS-treated chondrocytes from apoptosis acting as an interceptor of miR-498/mTOR cross-talking

Abstract

We aimed to investigate the regulation of circular RNAs in lipopolysaccharide (LPS)-treated chondrocytes isolated from SD rat. In this study, we analyzed how circFADS2 was regulated in LPS-treated chondrocytes and isolates from Rheumatoid arthritis (RA) patients and found that circFADS2 and mTOR were highly expressed whereas miR-498 expression was significantly reduced. We then silenced circFADS2 in LPS-treated chondrocytes; this resulted in a declined expression of type II collagen, but an increase in the expression of MMP-13, COX-2, and IL-6. Overall, silencing circFADS2 caused a significant reduction in the proliferative rate of LPS-treated chondrocytes, increased apoptotic levels, miR-498 upregulation, and mTOR downregulation. Dual-luciferase reporter assay indicated that circFADS2 directly targeted miR-498. In contrast, miR-498 down-regulation affected circFADS2 silencing, promoting extracellular matrix (ECM) degradation and apoptosis. The 3’ UTR of the mTOR gene is targeted by miR-498, and consequently, in cells transfected with miR-498, there was a significant reduction of mTOR expression at the protein and mRNA levels. Silencing mTOR had a similar effect to circFADS2 silencing on type II collagen, MMP-13, COX-2, and IL-6 expression, as well as cell proliferation and apoptosis. In conclusion, circFADS2 may affect LPS-induced chondrocytes properties by regulating the ECM catabolism, inflammation, and apoptosis in chondrocytes.

Circular RNA circFADS2 is Overexpressed in Sepsis and Suppresses LPS-Induced Lung Cell Apoptosis by Inhibiting the Maturation of miR-15a-5p

“…Consistently, circFADS2 can sponge miR-498 [13]. Interestingly, our data showed that circFADS2 could suppress the maturation of miR-15a-5p.…”

“…In another study, circFADS2 was reported to be upregulated in colorectal cancer and predicted the poor survival of patients [17]. Besides that, circFADS2 plays protective roles in LPS-treated chondrocytes by interacting with miR-498/mTOR axis [13]. In this study we rst showed the upregulation of circFADS2 in sepsis patients.…”

ABIN‐1 protects chondrocytes from lipopolysaccharide‐induced inflammatory injury through the inactivation of NF‐κB signalling

“…The data of this study were mainly obtained using LPS‐stimulated chondrocytes in vitro. Although LPS‐stimulated chondrocytes have been widely used as an in vitro model for the study of OA, this type of study cannot provide sufficient data to conclude that ABIN‐1 plays a vital role in the regulation of OA progression. Therefore, the precise role of ABIN‐1 in OA requires further validation using in vivo animal models.…”

CircRNA circFADS2 is Under-expressed in Sepsis and Protects Lung Cell From LPS-induced Apoptosis by Downregulating miR-133a

“…In lung cancer and colorectal cancer, circFADS2 is overexpressed and promotes cancer progression by regulating cancer cell behaviors, such as increasing cell proliferation and invasion [18,19]. Besides that, a recent study reported that circFADS2 could interact with miR-498/mTOR axis to protect chondrocyte from LPS-induced apoptosis [15]. It is well known that LPS-induced cell apoptosis and in ammation are critical contributors to sepsis [17], indicating the involvement of circFADS2 in sepsis.…”

“…Therefore, circRNAs are potential targets to treat diseases. It has been reported that circRNA circFADS2 and miR-133a play opposite roles in LPS-induced cell apoptosis [15,16], which contributes to the development of sepsis [17]. We therefore analyzed the involvement of circFADS2 and miR-133a in sepsis and explored the interactions between them.…”