Transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis

Cdk9 is a serine‐threonine protein kinase that has been recognized as a regulator of cardiac differentiation. Recently, we have reported that transient induction of Cdk9 using noncoding RNA targeting Cdk9 sequences results in efficient cardiac differentiation. Concerning Cdk9 regulatory roles, here, we proposed whether constant overexpression of Cdk9 might influence the differentiation of myoblast C2C12 cells into myotubes. We overexpressed Cdk9 in mouse myoblast C2C12 cells to investigate its regulatory roles on myogenic differentiation. Upon Cdk9 overexpression, the expression level of myogenic regulatory factors was determined. Moreover, the expression profile of three important myomiRs consist of miR 1, 133 and 206 was examined during the differentiation process. Although Cdk9 expression is necessary for inducing differentiation in the early stage of myogenesis, continuous Cdk9 expression inhibits differentiation by modulating myomiRs and myogenic gene expression. Our results indicate that the transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis. Cdk9, as a key player in cardiac differentiation, modulates the expression of myomiRs and myogenic factors. Cdk9 induces the myogenic genes expression including MyoD, Myogenin, and Mef2 and muscle‐specific microRNAs including miR‐1 and miR‐206 in the early stage of differentiation. However, decreased expression levels of Mef2, miR‐1, and miR‐133 were observed toward the late stage of myocyte differentiation following constant overexpression of Cdk9 in C2C12 cells. These results indicate that the transient induction of Cdk9 in the early stage of differentiation is critical for myogenesis.