Background: Cell division cycle associated 4 (CDCA4) has been reported to be engaged into the progression of several cancers. The function of CDCA4 in Non-small cell lung cancer (NSCLC) was unknown. We aimed to explore the critical role of CDCA4 in NSCLC.
Methods: CDCA4 stably knocking down and overexpression cell lines were established and Western blotting assay was applied to measure relevant protein expression of Epithelial-Mesenchymal Transtion (EMT) and cell autophagy. Staining of acidic vacuoles, transmission electron microscopy and immunofluorescence staining were employed to detect autophagy. The ability of cells to migrate and invade were detected by Transwell migration and invasion assays. The interaction of CDCA4 with CARM1 was identified by immunoprecipitation and Western blotting analysis.
Results: In the present study, it was found that inhibition of CDCA4 induced EMT, migration and invasion of NSCLC cells while inhibiting autophagy of NSCLC cells. Meanwhile, overexpression of CDCA4 in NSCLC cells showed the opposite function. More importantly, the inhibition of autophagy could promote the EMT, migration and invasion of NSCLC cells, which should be impaired via the activation of autophagy. In addition, CDCA4-inhibited EMT, migration and invasion could be partially aggravated by autophagy activator, rapamycin, and reversed by autophagy inhibitor, 3-MA. Correspondingly, the application of rapamycin or 3-MA to CDCA4 knockdown cells showed the opposite effects. Further investigation suggested that CDCA4 could interact with coactivator associated arginine methyltransferase 1 (CARM1). Autophagy was induced while cell migration and invasion were inhibited in CARM1 knockdown cells. CDCA4 could suppress the protein expression CARM1 and knocking down of CARM1 could alter cell autophagy, migratory and invasive abilities regulated by CDCA4.
Conclusion: All data indicated that CDCA4 inhibited the EMT, migration and invasion of NSCLC via interacting with CARM1 to modulate autophagy.
Keywords: Autophagy; CARM1; CDCA4; EMT; Migration and invasion; Non-small cell lung cancer.