MicroRNA-122 regulates caspase-8 and promotes the apoptosis of mouse cardiomyocytes

Abstract

Cardiomyocyte apoptosis plays key roles in the pathogenesis of heart diseases such as myocardial infarction. MicroRNAs are important regulators of gene expression, which are also involved in the regulation of cardiomyocyte apoptosis. However, cardiomyocyte apoptosis regulated by microRNA (miR)-122 is largely unexplored. The aim of this study focused on the role of miR-122 in cardiomyocyte apoptosis. Cardiomyocytes were isolated from neonatal mice and primarily cultured. MiR-122 mimic and inhibitor were transfected to cardiomyocytes and verified by qRT-PCR. Cell viability and apoptosis post-transfection were assessed by MTT assay and flow cytometry, respectively. Changes in expression of caspase-8 were quantified by qRT-PCR and western blot. Results showed that miR-122 mimic and inhibitor successfully induced changes in miR-122 levels in cultured cardiomyocytes (P<0.01). MiR-122 overexpression suppressed viability and promoted apoptosis of cardiomyocytes (P<0.05), and miR-122 knockdown promoted cell viability and inhibited apoptosis (P<0.05). The mRNA and protein levels of caspase-8 were elevated by miR-122 overexpression (P<0.01) and reduced by miR-122 knockdown (P<0.001). These results suggest an inductive role of miR-122 in cardiomyocyte apoptosis, which may be related to its regulation on caspase-8.

MicroRNA expression profiling in placenta and maternal plasma in early pregnancy loss

“…The invasion of maternal decidua to placenta trophoblasts is the most important stage in the normal physiological course of a normal pregnancy, and apoptosis has a critical role in normal placental development ( 50 ). MiR-122 may be involved in apoptosis in cancer cells ( 51 ). A different previous study demonstrated that miR-122 increased the expression of oncogenes cyclin G1 ( CCNG1 ) ( 52 ) and reduced the expression of a disintegrin and ADAM metallopeptidase domain 17, EGFR and FAK activation levels ( 53 ).…”

“…The genes targeted by the let-7 family have been identified as effective in embryonic stem cell and cardiovascular differentiation ( 59 ). Zhang et al determined the hypoxia-inducible factor 1α ( HIF1 α)/AGO1/VEGF, which are the factors related with let-7, have a role in the hypoxia-induced angiogenesis signaling pathway ( 51 ). HIF1 α is a key transcription factor, which upregulates the expression levels of let-7, and let-7 targets AGO1 , leading to the translational suppression of VEGF mRNA which has an important role in angiogenesis process ( 56 ).…”

KLF5 influences cell biological function and chemotherapy sensitivity through the JNK signaling pathway in anaplastic thyroid carcinoma

“…The correlation analysis of the genes expression level was done with the method. [ 24 ] Glyceraldehyde 3‐phosphate dehydrogenase was used as the endogenous control for standardization.…”

MicroRNA as a Therapeutic Target in Cardiac Remodeling

“…Interestingly, the activation of peroxisome proliferator-activated receptor (PPAR)- γ with pioglitazone abrogates proapoptotic effects of miR-29 and protects cardiac cells from death [98]. miR-122 promotes cardiac apoptosis by inhibiting blockers of caspase-8 and enhancing its expression [99]. Apart from this, miR-378 promotes cardiomyocyte apoptosis by blocking a survival signaling cascade activated by Akt pathway through inhibition of expression of insulin-like growth factor 1 receptor (IGF1R) [100].…”