Palmitic Acid-Induced miR-429-3p Impairs Myoblast Differentiation by Downregulating CFL2

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• MicroRNAs regulate skeletal myogenesis and maintenance.
• Cofilin-2 (CFL2) is essential for actin cytoskeleton dynamics and muscle cell differentiation.
• Mechanisms by which saturated fatty acids (SFAs) or obesity inhibit myogenesis remain unclear.

Purpose of the Study:

• To investigate the role of miR-429-3p in regulating CFL2 expression, actin dynamics, myoblast proliferation, and myogenic differentiation.
• To elucidate the impact of palmitic acid (PA), a common SFA, on these cellular processes.

Main Methods:

• Utilized C2C12 myoblast cell line.
• Administered palmitic acid (PA) to inhibit myogenic differentiation.
• Transfected cells with miR-429-3p mimic.
• Assessed CFL2 expression, actin filament formation, nuclear YAP levels, cell cycle progression, and expression of myogenic factors (MyoD, MyoG, MyHC).

Main Results:

• Palmitic acid inhibited myoblast differentiation, reduced CFL2, and induced miR-429-3p.
• miR-429-3p directly targeted the 3'UTR of CFL2 mRNA, suppressing its expression.
• miR-429-3p mimic promoted F-actin formation and nuclear YAP, enhancing cell proliferation.
• miR-429-3p mimic suppressed myogenic factors and impaired myogenic differentiation.

Conclusions:

• miR-429-3p plays a critical role in inhibiting myogenic differentiation by suppressing CFL2.
• SFAs can induce miRNAs that regulate actin dynamics and skeletal myogenesis.
• This study provides insights into miRNA-mediated regulation of muscle development in response to dietary factors.