Myosin Regulatory Light Chain Silencing: Function, Mechanisms, and Therapeutic Implications in Pancreatic Cancer

Pancreatic cancer is the most lethal of all cancers. Patients diagnosed with this disease die within six months 95% of the time. There is one currently known conventional chemotherapy for pancreatic cancer and it provides minimal benefits. This study's recent strategic efforts have focused on identifying and validating improved molecular targets against pancreatic cancer. In this study, the potential role of Myosin Regulatory Light Chain (MRCL3) in pancreatic cancer was evaluated. MRCL3 is a regulatory protein implicated in cytokinesis, receptor capping, and cell locomotion. The effect of silencing MRCL3 in BxPC3 cells was examined to determine whether endogenous MRCL3 promoted growth in pancreatic cancer cells. This study demonstrated that MRCL3 significantly inhibited the proliferation of these cells compared with the controls. Cells undergoing apoptosis (Sub G1) were measured after transfecting BxPC3 cells with MRCL3 siRNA to determine whether MRCL3 is also required for protecting pancreatic cancer cells from cell death. Knockdown of MRCL3 resulted in 10% increase in cell death in BxPC3 cells compared to the controls. The expression of AP-1 protein factors, c-Fos and c-Jun, were examined in BxPC3 cells to investigate how MRCL3 regulated cell fate. This study has shown that MRCL3 knockdown in these cells increased the expression of c-Jun while blocking c-Fos expression. These results imply that the MRCL3 pathway is mediated through AP-1 transcriptional factors. Given the lack of promising pancreatic cancer drugs, this study sheds several insights on possible targets that can lead to the treatment of this disease.