The Role And Mechanism Of WDR1 In Regulating The Migration And Proliferation In Non Small Cell Lung Cancer

Objective:Lung cancer is one of the most dangerous human malignant tumors in the world.Its high incidence and cure rate are the highest in malignant tumors.The main characteristics of cancer are cell invasion and migration which involves the coordination among various protein molecules,the interaction of cytoskeleton in migration and the actin dynamics.WDR1(WD-repeat domain 1)is a major cofactor of actin deploymerization factors ADF/cofilin,strongly accelerating ADF/cofilin-mediated actin disassembly.At present,the role of WDR1 in the progress of non-small cell lung cancer(NSCLC)has not yet been reported.The result of RT-PCR experiment shows that the expression level of WDR1 in human non-small cell lung cancer tissues increased significantly compared with adjacent non tumor tissues,and the high expression of WDR1 was associated with the poor prognosis of patients with non-small cell lung cancer.Based on the above analysis,we systematically studied and analyzed the biological functions of WDR1 in non-small cell lung cancer.We used the technology of shRNA interference and overexpression to down regulation and highly express WDR1 in A549 and H1299 cells,found that knockdown of WDR1 significantly inhibited the process of proliferation,migration,invasion and EMT in non-small cell lung cancer cells.However,overexpression of WDR1 promoted proliferation and migration in non-small cell lung cancer cells.The experiment of xenograft tumor models was constructed,and the results of the experiment were in agreement with the results of cell experiments in vitro.Through further mechanism study showed that WDR1 regulated the movement ability and cell connection of tumor cells by promoting ADF/cofilin mediated actin depolymerization to promote the metastasis of nonsmall cell lung cancer.Our results suggest that the specific inhibitors of ADF/cofilinWDR1-actin are expected to become the new target for NSCLC.