Myeloid leukemia factor-1 is a novel modulator of neonatal rat cardiomyocyte proliferation

The present study focuses on the identification of the gene expression profile of neonatal rat cardiomyocytes (NRVCMs) after dynamic mechanical stretch through microarrays of RNA isolated fromcells stretched for 2, 6 or 24 h. In this analysis,myeloid leukemia factor-1 (MLF1) was found to be significantly downregulated during the course of stretch.We found that MLF1 is highly expressed in the heart, however, its cardiac function is un- known yet. In linewithmicroarray data,MLF1was profoundly downregulated in in vivomousemodels of cardio- myopathy, and also significantly reduced in the hearts of human patientswith dilated cardiomyopathy. Our data indicates that the overexpression ofMLF1 in NRVCMs inhibited cell proliferation while augmenting apoptosis. Conversely, knockdown ofMLF1 protected NRVCMs fromapoptosis and promoted cell proliferation.Moreover, wefound that knockdown ofMLF1 protectedNRVCMs fromhypoxia-induced cell death. The observed accelerat- ed apoptosis is attributed to the activationof caspase-3/-7/PARP-dependent apoptotic signaling and upregulation of p53.Most interestingly, MLF1 knockdown significantly upregulated the expression of D cyclins suggesting its possible role in cyclin-dependent cell proliferation. Taken together,we, for the first time, identified an important role forMLF1 in NRVCMproliferation.