MicroRNA-197 regulates chondrocyte proliferation, migration, and inflammation in pathogenesis of osteoarthritis by targeting EIF4G2

Abstract

Recent studies have demonstrated that microRNAs (miRNAs) are involved in many pathological conditions including osteoarthritis (OA). In this study, we aimed to investigate the role of miR-197 in OA and the potential molecular mechanism. The expression levels of miR-197 was detected by quantitative real-time PCR analysis. Cell proliferation and migration abilities were performed by MTT and transwell assays. The concentrations of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were detect using ELISA assay. Furthermore, luciferase reporter and rescue assays were applied to identify the functional target gene of miR-197 in OA. The results showed that miR-197 expression was significantly downregulated in the OA cartilage tissues compared with normal cartilage tissues, accompanied by upregulation of EIF4G2 expression. An inverse correlation was found between EIF4G2 and miR-197 expressions in OA cartilage tissues. Treatment with miR-197 mimics promoted the growth and migration abilities of chondrocytes, while miR-197 inhibitors induced the opposite effects. Furthermore, restoration of miR-197 significantly decreased IL-1β, IL-6, and TNF-α expression, whereas knockdown of miR-197 led to a induction in these inflammatory mediators. Moreover, EIF4G2 was predicted and confirmed as a directly target of miR-197. Overexpressed miR-197 could downregulate EIF4G2 expression in chondrocytes, while miR-197 knockdown could elevate EIF4G2 expression. Additionally, EIF4G2 overexpression reversed the effects of miR-197 mimics on chondrocytes proliferation, migration and inflammation. Taken together, our study demonstrated that miR-197 promotes chondrocyte proliferation, increases migration, and inhibits inflammation in the pathogenesis of OA by targeting EIF4G2, indicating the potential therapeutic targets of the miR-197/EIF4G2 axis for OA treatment.

Sinomenine suppressed keratinocyte proliferation and imiquimod-induced psoriasis-like dermatitis by regulating lncRNA XIST

“…EIF4G2 is an important mediator of translation initiation and plays an important role in the process of cell mitosis [35]. It has been reported that EIF4G2 affects chondrocyte inflammation [36]. Our study found that XIST interacted with EIF4G2 to affect the inflammatory response, and lncRNA XIST attenuated MDM2-mediated ubiquitination and degradation of EIF4G2.…”

Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells via the miR-101-3p/EIF4G2 Axis

“…EIF4G has two functional homologs in mammals, namely, EIF4G1 and EIF4G2 (Caron et al, 2004). EIF4G2 expression is promoted in osteoarthritis cartilage tissues, and EIF4G2 may be implicated in the pathogenesis of osteoarthritis (Gao S. et al, 2020). Nevertheless, the role of EIF4G2 in IDD remained unknown, and this study filled this gap to a certain extent.…”

“…To further determine the downstream target of miR-101-3p-mediated ECM remodeling, we conducted follow-up experiments. EIF4G2 is abnormally expressed in osteoarthritis (Gao S. et al, 2020). The binding site between miR-101-3p and EIF4G2 was predicted by using the Starbase database (Figure 4A).…”

miR-379-5P INHIBITION ENHANCES INTESTINAL EPITHELIAL PROLIFERATION AND BARRIER FUNCTION RECOVERY AFTER ISCHEMIA/REPERFUSION BY TARGETING EIF4G2

“…Cell cycle research revealed that EIF4G2 silencing led to a rise in cells in the G0/G1 phase and a drop in cells in the G2/M phase (36). EIF4G2 promotes cell proliferation in a variety of tissues, such as chondrocytes and ovarian cancer (37)(38)(39). EIF4G2 has also been proven to have a strong proliferative effect on human colon cancer cells, and its expression is increased in skeletal muscle after I/R (36,40).…”