Identification of apoptosis-related microRNAs and their target genes in myocardial infarction post-transplantation with skeletal myoblasts.
BACKGROUND
Skeletal myoblasts (SkMs) has provided a promising treatment for myocardial infarction (MI). Functioning as posttranscriptional regulators, microRNAs (miRNAs) play important roles in cardiac repairment and stem cell regulation. However, the correlation between miRNAs and their targeted genes in SkM cell therapy for MI was not fully understood.


METHODS
We explored the cardioprotection by SkMs in infracted rats and determined cardiac functions at 4 weeks. In addition, we compared the expression profiles of miRNAs and mRNAs in post-MI rats with or without SkM cell therapy using microarray. The concordance between miRNA expression and mRNA levels of potential target genes was confirmed by quantitative real-time PCR.


RESULTS
Quantitative echocardiography and histology showed improved cardiac function, attenuated heart infarcted area and inhibited cardiomyocyte apoptosis in the SkM group, compared with MI group. We identified that 160 miRNAs were differentially expressed in MI group as compared to the control group and 78 miRNAs were differentially expressed in the SkM treated group as compared to the untreated post-MI. We focused on a novel set of apoptosis-associated miRNAs and their target genes, among which 4 miRNAs (miR-30a-5p, miR-30c-5p, miR-145-5p, miR-140-3p), except one (miR-143-3p), were downregulated in the SkM treated group as compared to the untreated group. Furthermore, we found seven genes including Angptl4, Dpep1, Egr1, Eif5a, Tsc22d3, Irs2 and Cebpb that showed a linear correlation with which miRNAs.


CONCLUSIONS
The downregulation of apoptosis-regulatory miRNAs and in turn upregulation of target genes may partially account for rescue effect of SKM therapy for MI.
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. doctorliu9128@126.com.|Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. doctorliu9128@126.com.
Qi
Q
Liu
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. duguoqing9@163.com.|Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. duguoqing9@163.com.
Guo Qing
GQ
Du
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. zzt405zzt405@163.com.|Department of Cardiac Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. zzt405zzt405@163.com.
Zhi Tao
ZT
Zhu
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. 289986993@qq.com.|Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. 289986993@qq.com.
ChunYang
C
Zhang
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. sunxiaowei198902@163.com.|Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. sunxiaowei198902@163.com.
Xiao Wei
XW
Sun
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. 190821918@qq.com.|Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. 190821918@qq.com.
Jing Jin
JJ
Liu
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. xialiyinmingzhu@126.com.|Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. xialiyinmingzhu@126.com.
Xia
X
Li
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. wys19874642163@yahoo.com.cn.|Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. wys19874642163@yahoo.com.cn.
Yong Shun
YS
Wang
The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China. duwenjuan8009@126.com.|Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China. duwenjuan8009@126.com.
Wen Juan
WJ
Du
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D004452:Echocardiography; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology*; D032448:Myoblasts, Skeletal / Q000378:metabolism* / Q000637:transplantation*; D009203:Myocardial Infarction / Q000150:complications*; D020411:Oligonucleotide Array Sequence Analysis; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
D035683:MicroRNAs