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

Area of Science:

• Muscle biology
• Molecular genetics
• Biochemistry

Background:

• Myogenic factor D (Mdfi) is crucial for myoblast development and muscle fiber type transformation.
• The precise regulatory network governed by Mdfi in myoblasts remains largely unelucidated.

Purpose of the Study:

• To investigate the regulatory network of Mdfi in myoblasts.
• To identify microRNAs (miRNAs) and genes involved in Mdfi-mediated muscle development and fiber type transformation.

Main Methods:

• Performed microRNA sequencing (miRNA-seq) on Mdfi-overexpressing (Mdfi-OE) and wild-type (WT) C2C12 myoblast cells.
• Conducted comparative analyses to identify differentially expressed miRNAs (DEMs).
• Utilized enrichment analysis and constructed miRNA-mRNA interaction networks.

Main Results:

• Identified 66 differentially expressed miRNAs between Mdfi-OE and WT cells.
• DEMs are implicated in myoblast differentiation and muscle fiber type transformation via signaling pathways including MAPK, Wnt, PI3K-Akt, mTOR, and calcium signaling.
• Discovered ten hub miRNAs and five hub genes in myogenic differentiation networks, and eight hub miRNAs and eleven hub genes in muscle fiber type transformation networks.
• Highlighted three specific miRNAs (miR-335-3p, miR-494-3p, miR-709) potentially regulating both processes.

Conclusions:

• Mdfi exerts regulatory control over myoblast differentiation and muscle fiber type transformation through specific miRNA networks.
• Identified hub miRNAs and genes may serve as critical biomarkers for muscle and metabolic diseases.
• The findings provide novel insights into the molecular mechanisms underlying muscle development and disease.