WD40 Repeat 43(WDR43)mediates Proliferation,apoptosis And Invasion Via Vimentin In Colorectal Cancer

Background: WD40 repeat protein 43(WDR43)is an RNA-binding protein that belongs to the WD40 repeat(WDR)domain protein.Its biological function is largely undeveloped,especially in colorectal cancer(CRC).This study aims to explore the effects of WDR43 on the biological behavior like proliferation,apoptosis and migration of colorectal cancer cells in vivo and in vitro.Methods: By searching The Cancer Genome Atlas(TCGA)database,the correlation between WDR43 expression and the occurrence and development of CRC was found.The expression of WDR43 in 16 patients with CRC in Nanjing Gulou Hospital was detected by immunohistochemistry(IHC)technology.After the knockdown of WDR43 by lentivirus in two CRC cell lines,cell proliferation was evaluated by MTT,Celigo and colony formation assay while cell apoptosis was detected by flow cytometry,and cell migration and invasion was determined by Transwell experiment.Then,Western Blotting(WB)was used to detect a variety of potential downstream functional proteins and signal pathways.Using lentivirus to overexpress vimentin(VIM)to study the effect of overexpression of VIM on the biological function of CRC cells after WDR43 silence.Finally,a subcutaneous xenotransplantation model of nude mouse was established to further explore the role of WDR43 in vivo.Results: TCGA data showed that WDR43 is highly expressed in CRC tissues,which is related to the staging and histological subtypes of CRC.The immunohistochemical detection of specimens from 16 patients with colorectal cancer confirmed that the expression of WDR43 was elevated in CRC.Silencing WDR43 can increase the apoptosis of colorectal cancer cells in vitro,and inhibit the proliferation,migration and invasion of colorectal cancer cells.The results of WB showed that the expression of VIM was inhibited due to WDR43 knockdown.Overexpression of VIM could partially reverse the effect of WDR43 silencing on the proliferation and migration of colorectal cancer cells.The subcutaneous tumor model of nude mouse further confirmed the inhibitory effect of knockdown WDR43 on the growth of colorectal cancer and the recovery effect of overexpression of VIM.Conclusion: WDR43 is highly expressed in CRC cells and tissues,and it mediates the biological functions of colorectal cancer cells such as apoptosis,migration,invasion and metastasis through VIM.This study discovered and explained the positive role of WDR43 in the occurrence and development of CRC.It may serve as a valuable biomarker to provide new ideas for the diagnosis and treatment of colorectal cancer.