miR-484 targeting of Yap1-induced LPS-inhibited proliferation, and promoted apoptosis and inflammation in cardiomyocyte

Abstract

Apoptosis and inflammation were the main hallmarks of sepsis-induced cardiomyopathy (SIC). Yes-associated protein isoform 1 (Yap1) and miR-484 were involved in mitochondrial fission and apoptosis, especially proapoptotic roles in SIC. Here, we investigated the role of Yap1 and miR-484 in lipopolysaccharide (LPS)-treated H9c2 cells. Yap1 was downregulated, while miR-484 was elevated by LPS treatment. Cell counting kit-8, flow cytometry, western blotting, and ELISA showed that miR-484 inhibitor significantly improved cell viability, decreased apoptosis, suppressed NLRP3 inflammasome formation, and reduced secretion of inflammatory cytokines TNF-α, IL-1β, and IL-6. Yap1, directly targeted by miR-484 shown in the luciferase assay, was more like a compensatory regulator of LPS stimulation. Knockdown of Yap1 inverted the effects of miR-484 inhibitor, including decreased cell viability, and promoted apoptosis and inflammation. These revealed miR-484 directly targeted mRNA of Yap1 to inhibit cell viability, and promote apoptosis and inflammation in LPS-treated H9c2 cells.

miR-484: A Potential Biomarker in Health and Disease

“…Interestingly, LPS treatment of H9C2 cells promoted miR-484 to negatively regulate YAP1 expression. Interestingly, LPS treatment of H9C2 cells promoted miR-484 to negatively regulate YAP1 expression ( 34 ) ( Table 2 ) . miR-484 inhibitor significantly improved LPS-induced cell viability and apoptosis, whereas YAP1 knockdown reversed the effect of miR-484 inhibitor ( 34 ).…”

“…Interestingly, LPS treatment of H9C2 cells promoted miR-484 to negatively regulate YAP1 expression ( 34 ) ( Table 2 ) . miR-484 inhibitor significantly improved LPS-induced cell viability and apoptosis, whereas YAP1 knockdown reversed the effect of miR-484 inhibitor ( 34 ). YAP1, a key downstream regulatory target in the Hippo pathway, is closely associated with immune disorders and inflammatory diseases ( 91 ).…”

“…In both clinical PC specimens and pancreatic ductal adenocarcinoma cell lines, high levels of consistent lncRNA THAP9-AS1 expression were observed, which competitively inhibited the negative regulatory effect of miR-484 on YAP and thus accelerated the proliferation of pancreatic ductal adenocarcinoma cells ( 30 ). Moreover, miR-484 directly induced downregulation of YAP1 expression involved in apoptosis and inflammatory response in cardiomyocytes ( 34 ) ( Table 3 ) . Similarly, Ma et al.…”

Mir-484 contributes to diminished ovarian reserve by regulating granulosa cell function via YAP1-mediated mitochondrial function and apoptosis

“…The relationship between miR-484 and YAP1 has been previously reported. Xu et al found that miR-484 directly targets the mRNA of YAP1 to inhibit cell viability, promoting the inflammatory response and apoptosis in LPS-treated cardiomyocytes 41 . Consistent with these observations, our data showed that si-YAP1 treatment decreased proliferation and induced apoptosis in GCs.…”

Yes-Associated Protein and Transcriptional Coactivator with PDZ-Binding Motif in Cardiovascular Diseases

“…However, the overexpression of miR-29 does not induce CMs hypertrophy in neonatal rats [ 39 ]. Alternatively, miR-484 directly targets the YAP to suppress the cell viability and promote the NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome and the production of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), increasing apoptosis in H9c2 cells [ 45 ].…”