Lentivirus-mediated short hairpin RNA interference of CENPK inhibits growth of colorectal cancer cells with overexpression of Cullin 4A  

作　　者：Xian Li Yi-Ru Han Xuefeng Xuefeng Yong-Xiang Ma Guo-Sheng Xing Zhi-Wen Yang Zhen Zhang Lin Shi Xin-Lin Wu 

机构地区：[1]Clinical Medical Research Center,The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China [2]Department of Gastrointestinal Surgery,The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China [3]Department of Pathology,The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China

出　　处：《World Journal of Gastroenterology》2022年第37期5420-5443,共24页世界胃肠病学杂志（英文版）

基　　金：the National Natural Science Foundation of China,No.81860416 and No.22168028;Inner Mongolia Autonomous Region Grassland Talent Innovation Talent Team Fund,No.2019;Inner Mongolia Natural Science Fund,No.2021MS02005.

摘　　要：BACKGROUND Colorectal cancer(CRC)is one of the most common malignant tumors worldwide.The identification of novel diagnostic and prognostic biomarkers for CRC is a key research imperative.Immunohistochemical analysis has revealed high expression of centromere protein K(CENPK)in CRC.However,the role of CENPK in the progression of CRC is not well characterized.AIM To evaluate the effects of knockdown of CENPK and overexpression of Cullin 4A(CUL4A)in RKO and HCT116 cells.METHODS Human colon cancer samples were collected and tested using a human gene expression chip.We identified CENPK as a potential oncogene for CRC based on bioinformatics analysis.In vitro experiments verified the function of this gene.We investigated the expression of CENPK in RKO and HCT116 cells using quantitative polymerase chain reaction(qPCR),western blot,and flow cytometry.The effect of short hairpin RNA(shRNA)virus-infected RKO cells on tumor growth was evaluated in vivo using quantitative analysis of fluorescence imaging.To evaluate the effects of knockdown of CENPK and overexpression of CUL4A in RKO and HCT116 cells,we performed a series of in vitro experiments,using qPCR,western blot,MTT assay,and flow cytometry.RESULTS We demonstrated overexpression of CENPK in human colon cancer samples.CENPK was an independent risk factor in patients with CRC.The downstream genes FBX32,CUL4A,and Yesassociated protein isoform 1 were examined to evaluate the regulatory action of CENPK in RKO cells.Significantly delayed xenograft tumor emergence,slower growth rate,and lower final tumor weight and volume were observed in the CENPK short hairpin RNA virus infected group compared with the CENPK negative control group.The CENPK gene interference inhibited the proliferation of RKO cells in vitro and in vivo.The lentivirus-mediated shRNA interference of CENPK inhibited the proliferation of RKO and HCT116 colon cancer cells,with overexpression of the CUL4A.CONCLUSION We indicated a potential role of CENPK in promoting tumor proliferation,and it may be a novel d

关 键 词：Colorectal cancer Centromere protein K Bioinformatics analysis Lentivirus-mediated short hairpin RNA interference Cullin 4A 

分 类 号：R735.34[医药卫生—肿瘤]