MiR-29a Family as a Key Regulator of Skeletal Muscle Dysplasia in a Porcine Model of Intrauterine Growth Retardation.

MiR-29a Family as a Key Regulator of Skeletal Muscle Dysplasia in a Porcine Model of Intrauterine Growth Retardation.
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MiR-29a 家族作为宫内生长迟缓猪模型中骨骼肌发育不良的关键调节因子

DOI:
10.3390/biom12091193
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发表时间:
2022-08-28
期刊:
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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MicroRNAs(MiRNAs)在许多生物过程中发挥着重要的作用。本研究通过测序鉴定了正常和宫内发育迟缓(IUGR)新生仔猪骨骼肌中的miRNAs,并在体外验证了规范的miRNAs的功能。在新生仔猪骨骼肌中共检测到403个miRNAs,其中IUGR猪表达上调的miRNAs为30个,下调的为46个。上调的miRNAs主要集中在丙酸代谢、内吞作用、β-丙氨酸代谢、缝隙连接和肿瘤坏死因子信号转导途径。下调的miRNAs主要集中在化学致癌-受体激活、内吞作用、MAPK信号通路、胰岛素抵抗和EGFR酪氨酸激酶抑制剂抵抗。对脐带血和骨骼肌miRNAs的共表达网络分析表明,miR-29家族是IUGR猪必不可少的调节因子。双荧光素酶报告系统显示IGF1和CCND1是miR-29家族的靶基因。IUGR、猪脐血外切体和miR-29a模拟基因转染可明显抑制细胞增殖,促进细胞蛋白降解标记基因Fbxo32和Trim63的表达。综上所述,这些结果丰富了涉及IUGR动物骨骼肌发育的miRNAs调控网络。
MicroRNAs (miRNAs) play an essential role in many biological processes. In this study, miRNAs in the skeletal muscle of normal and intrauterine growth retardation (IUGR) neonatal piglets were identified by sequencing, and canonical miRNAs were functionally validated in vitro. A total of 403 miRNAs were identified in neonatal piglet skeletal muscle, among them 30 and 46 miRNAs were upregulated and downregulated in IUGR pigs, respectively. Upregulated miRNAs were mainly enriched in propanoate metabolism, endocytosis, beta-Alanine metabolism, gap junction, and tumor necrosis factor signaling pathway. Down-regulated miRNAs were mainly enriched in chemical carcinogenesis—receptor activation, endocytosis, MAPK signaling pathway, insulin resistance, and EGFR tyrosine kinase inhibitor resistance. Co-expression network analysis of umbilical cord blood and skeletal muscle miRNAs showed that the miR-29 family is an essential regulator of IUGR pigs. The dual-luciferase reporter system showed that IGF1 and CCND1 were target genes of the miR-29 family. Transfection of IUGR pig umbilical cord blood exosomes and miR-29a mimic significantly inhibited cell proliferation and promoted the expression of cellular protein degradation marker genes Fbxo32 and Trim63. In summary, these results enrich the regulatory network of miRNAs involved in skeletal muscle development in IUGR animals.
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