An eIF3a gene mutation dysregulates myocardium growth with left ventricular noncompaction via the p-ERK1/2 pathway

作者全名："Ge, Mei; Bai, Xuehan; Liu, Aoyi; Liu, Lingjuan; Tian, Jie; Lu, Tiewei"

作者地址："[Ge, Mei; Bai, Xuehan; Liu, Aoyi; Liu, Lingjuan; Tian, Jie; Lu, Tiewei] Chongqing Med Univ, Dept Cardiol, Childrens Hosp, Chongqing 401122, Peoples R China; [Ge, Mei; Bai, Xuehan; Liu, Aoyi; Liu, Lingjuan; Tian, Jie; Lu, Tiewei] Minist Educ, Chongqing Key Lab Pediat, China Int Sci & Technol Cooperat Ctr Child Dev &, Key Lab Child Dev & Disorders, Chongqing 401122, Peoples R China"

通信作者："Lu, TW (corresponding author), Chongqing Med Univ, Dept Cardiol, Childrens Hosp, Chongqing 401122, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000661449300014

JCR分区：Q1

影响因子：6.8

年份：2021

卷号：8

期号：4

开始页：545

结束页：554

文献类型：Article

关键词：Differentiation; eIF3a mutation; Left ventricular non-compaction (LVNC); Migration; p-ERK1/2; Proliferation

摘要："Left ventricular noncompaction (LVNC) is a heterogeneous disorder with unclear genetic causes and an unknown mechanism. eIF3a, an important member of the Eukaryotic translation initiation factor 3 (eIF3) family, is involved in multiple biological processes, including cell proliferation and migration during myocardial development, suggesting it could play a role in LVNC development. To investigate the association between a novel variant (c.1145 A- > G) in eIF3a and LVNC, and explore potential mechanisms that could lead to the development of LVNC. A novel eIF3a variant, c.1145 A- > G, was identified by whole-exome sequencing in a familial pedigree with LVNC. Adenovirus vectors containing wild-type eIF3a and the mutated version were constructed and co-infected into H9C2 cells. Cell proliferation, apoptosis, cell migration, and differentiation, as well as phosphorylation of ERK1/2 were studied and were measured by proliferation assays, flow cytometry, real-time PCR and Western blot, respectively. The eIF3a mutation inhibited the proliferation of H9C2 cells, induced apoptosis, promoted cell migration, and inhibited the differentiation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The effect of the eIF3a mutation may be attributed to a decrease in expression of p-ERK1/2. A novel eIF3a gene mutation disrupted the p-ERK1/2 pathway and caused decreased myocardium proliferation, differentiation, accelerated migration.This finding may provide some insight into the mechanism involved in LVNC development. Copyright (C) 2020, Chongqing Medical University. Production and hosting by Elsevier B.V."

基金机构：National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570218]

基金资助正文：This work was supported by the National Natural Science Foundation of China [grant number: 81570218].