miR-218 suppresses cardiac myxoma proliferation by targeting myocyte enhancer factor 2D

Abstract

The role of microRNA-92b-3p (miR-92b-3p) in cardiac hypertrophy was not well illustrated. The present study aimed to investigate the expression and potential target of miR-92b-3p in angiotensin II (Ang-II)-induced mouse cardiac hypertrophy. MiR-92b-3p was markedly decreased in the myocardium of Ang-II-infused mice and of patients with cardiac hypertrophy. However, miR-92b-3p expression was revealed increased in Ang-II-induced neonatal mouse cardiomyocytes. Cardiac hypertrophy was shown attenuated in Ang-II-infused mice received tail vein injection of miR-92b-3p mimic. Moreover, miR-92b-3p inhibited the expression of atrial natriuretic peptide (ANP), skeletal muscle α-actin (ACTA1) and β-myosin heavy chain (MHC) in Ang-II-induced mouse cardiomyocytes in vitro. Myocyte-specific enhancer factor 2D (MEF2D), which was increased in Ang-II-induced mouse hypertrophic myocardium and cardiomyocytes, was identified as a target gene of miR-92b-3p. Functionally, miR-92b-3p mimic, consistent with MEF2D siRNA, inhibited cell size increase and protein expression of ANP, ACTA1 and β-MHC in Ang-II-treated mouse cardiomyocytes. Taken together, we demonstrated that MEF2D is a novel target of miR-92b-3p, and attenuation of miR-92b-3p expression may contribute to the increase of MEF2D in cardiac hypertrophy.

Tumor-suppressing roles of miR-214 and miR-218 in breast cancer

“…Previous studies have already demonstrated that the miR-214 could suppress oncogenesis of bladder cancer by targeting the p53 and DNA damage-regulated protein 1 (PDRG1) ( 35 ), inhibit the progression of hepatocellular carcinoma by regulating β-catenin ( 36 , 37 ), also mediating cell proliferation by targeting ERK ( 38 ), mitochondrial transcription factor A (TFAM) ( 39 ) and ADP-ribosylation factor-like protein 2 (ARL2) ( 40 ). The miR-218 suppresses lung cancer and cardiac myxoma cell growth by reducing myocyte enhancer factor 2D (MEF2D) ( 41 , 42 ), inhibits glioma cells proliferation by inactivation of cyclin D1 ( 43 ) pathway and directly target E2F2 ( 24 ), reduces bladder cancer and esophageal squamous cells proliferation by targeting BMI-1 ( 34 , 44 ). The above evidence supports our conclusion.…”

MEF2 signaling and human diseases

“…Many recent studies observed that microRNAs, a type of small non-coding RNAs, participate in the regulation of MEF2s, especially in the progression of malignant diseases. miR-218 regulates MEF2D expression by targeting 3’UTR of its mRNA and down-regulation of miR-218 in cardiac myxoma condition can increase MEF2D expression and promote cell cycle progression [ 78 ]. In glioma cells, miR-18a binds with 3'UTR of MEF2D mRNA and negatively regulates its expression [ 79 ].…”

miR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma

“…Numerous studies have been performed on the role and related mechanism of miRNAs in numerous different kinds of diseases (9)(10)(11)(12). miRNAs bind primarily to the 3'-untranslated region (3'UTR) of their target messenger RNAs (mRNAs) to reduce their stability and decrease the expression of target mRNAs at the post-transcriptional level (13), which play important roles in various biological processes including cell growth, proliferation, differentiation and death (14)(15)(16)(17)(18)(19). Concerning chemotherapy in various types of cancers such as breast cancer, lung adenocarcinoma, glioblastoma, and ovarian cancer, recent studies have shown that miRNAs also act in important roles (20)(21)(22)(23)(24).…”