MLF1 protein is a potential therapy target for lung adenocarcinoma

Myeloid leukemia factor 1 (MLF1) is a protein involved in myeloid cell differentiation which regulates the cell cycle and the expression of numerous genes. The role of MLF1 in hematologic cancers is well established; however, its role in lung adenocarcinoma is unknown. Here, we investigated the role of MLF1 in lung adenocarcinoma using a variety of cell lines along with patient samples to determine whether MLF1 plays a significant role in this devastating disease. Lung cancer cell lines (A549, H1975, HCC827, and NCI-H460) and primary lung tissue were used to assess the relative levels of MLF1 in lung adenocarcinoma. The lung adenocarcinoma cell line A549 was infected with a lentivirus to knockdown MLF1, and successful knockdown was confirmed by a real-time polymerase chain reaction (qPCR). Cell proliferation was assessed through fluorescence imaging and MTT assays. Cell cycle analysis was performed utilizing flow cytometry and formation of cell colonies evaluated microscopically. Proliferation of A549 cells was significantly inhibited in cells where MLF1 was silenced compared to controls. Cell cycle analysis indicated that cell cycle phases were not significantly changed upon the silencing of MLF1 in lung adenocarcinoma cells. A significant increase in apoptosis was observed in MLF1-knockdown cells, while a significant decrease in the number of cell colonies formed was observed in MLF1-knockdown cells compared to controls. In most, but not all, human lung adenocarcinoma tissue samples, MLF1 was upregulated. The results show that MLF1 promotes the proliferation and colony forming abilities of lung adenocarcinoma cells and significantly decreases apoptosis while having no impact on the cell cycle. Further studies with larger sample sizes are needed 1) to conclude whether human lung adenocarcinoma upregulates MLF1, 2) to reveal the mechanism of action for MLF1 in lung carcinogenesis and 3) to investigate MLF1 gene therapy for the treatment of lung adenocarcinoma.