Putative MicroRNA-mRNA Networks Upon Mdfi Overexpression in C2C12 Cell Differentiation and Muscle Fiber Type Transformation

Bo Huang; Yiren Jiao; Yifan Zhu; Zuocheng Ning; Zijian Ye; Qing X Li; Chingyuan Hu; Chong Wang

doi:10.3389/fmolb.2021.675993

Putative MicroRNA-mRNA Networks Upon Mdfi Overexpression in C2C12 Cell Differentiation and Muscle Fiber Type Transformation

Front Mol Biosci. 2021 Oct 19:8:675993. doi: 10.3389/fmolb.2021.675993. eCollection 2021.

Authors

Bo Huang¹, Yiren Jiao¹, Yifan Zhu¹, Zuocheng Ning¹, Zijian Ye¹, Qing X Li², Chingyuan Hu³, Chong Wang¹

Affiliations

¹ National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, Guangdong Laboratory for Lingnan Modern Agriculture, College of Animal Science, South China Agricultural University, Guangzhou, China.
² Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu, HI, United States.
³ Department of Human Nutrition, Food and Animal Sciences, University of Hawaii at Manoa, Honolulu, HI, United States.

Abstract

Mdfi, an inhibitor of myogenic regulatory factors, is involved in myoblast myogenic development and muscle fiber type transformation. However, the regulatory network of Mdfi regulating myoblasts has not been revealed. In this study, we performed microRNAs (miRNAs)-seq on Mdfi overexpression (Mdfi-OE) and wild-type (WT) C2C12 cells to establish the regulatory networks. Comparative analyses of Mdfi-OE vs. WT identified 66 differentially expressed miRNAs (DEMs). Enrichment analysis of the target genes suggested that DEMs may be involved in myoblast differentiation and muscle fiber type transformation through MAPK, Wnt, PI3K-Akt, mTOR, and calcium signaling pathways. miRNA-mRNA interaction networks were suggested along with ten hub miRNAs and five hub genes. We also identified eight hub miRNAs and eleven hub genes in the networks of muscle fiber type transformation. Hub miRNAs mainly play key regulatory roles in muscle fiber type transformation through the PI3K-Akt, MAPK, cAMP, and calcium signaling pathways. Particularly, the three hub miRNAs (miR-335-3p, miR-494-3p, and miR-709) may be involved in both myogenic differentiation and muscle fiber type transformation. These hub miRNAs and genes might serve as candidate biomarkers for the treatment of muscle- and metabolic-related diseases.

Keywords: C2C12 cell differentiation; Mdfi; MiRNA-mRNA interaction network; hub gene; hub microRNA; muscle fiber type transformation.