More and more patients with advanced colorectal cancer(CRC)have benefited from surgical resection or ablation following neoadjuvant chemoradiotherapy(nCRT),but nCRT may be ineffective and have potential risks to some patients.Therefore,it is necessary to discover effective biomarkers for predicting the nCRT efficacy in CRC patients.Chromokinesin Kif4A plays a critical role in mitosis,DNA damage repair and tumorigenesis,but its relationship with nCRT efficacy in advanced CRC remains unclear.Here,we find that Kif4A expression in pretreated tumor tissue is positively correlated with poorer tumor regression after receiving nCRT(P=0.005).Knockdown of endogenous Kif4A causes an increased sensitivity of CRC cells to chemotherapeutic drugs 5-fluorouracil(5-FU)and Cisplatin(DDP),while overexpression of Kif4A enhances resistance of CRC cells to the chemotherapeutic drugs.Furthermore,depending on its motor domain and tail domain,Kif4A regulates DNA damage response(DDR)induced by 5-FU or DDP treatment in CRC cells.In conclusion,we demonstrate that Kif4A may be a potential independent biomarker for predicting the nCRT efficacy in advanced CRC patients,and Kif4A regulates chemosensitivity of CRC cells through controlling DDR.

Rui Zhang;Shuanghui Liu;Bojiang Gong;Wenran Xie;Youjuan Zhao;Liang Xu;Yi Zheng;Shengnan Jin;Chunming Ding;Chang Xu;Zhixiong Dong

Zhejiang Provincial Key Laboratory of Medical Genetics,Key Laboratory of Laboratory Medicine,Ministry of Education,School of Laboratory Medicine and Life Science,Wenzhou Medical University,Wenzhou 325000,China;Department of Colorectal Surgery,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China

生物化学与生物物理学报（英文版）

[1]Rui Zhang;Shuanghui Liu;Bojiang Gong;Wenran Xie;Youjuan Zhao;Liang Xu;Yi Zheng;Shengnan Jin;Chunming Ding;Chang Xu;Zhixiong Dong-.Kif4A mediates resistance to neoadjuvant chemoradiotherapy in patients with advanced colorectal cancer via regulating DNA damage response)[J].生物化学与生物物理学报（英文版）,2022(07):940-951

Kif4A,Chromokinesin,chemosensitivity

mediates,resistance,neoadjuvant,chemoradiotherapy,patients,advanced,colorectal,cancer,via,regulating,damage,response,More,CRC,have,benefited,from,surgical,resection,ablation,following,nCRT,but,may,ineffective,potential,risks,some,Therefore,necessary,discover,biomarkers,predicting,efficacy,plays,critical,role,mitosis,repair,tumorigenesis,its,relationship,remains,unclear,Here,we,find,that,pretreated,tissue,positively,correlated,poorer,regression,after,receiving,Knockdown,endogenous,causes,increased,cells,chemotherapeutic,drugs,fluorouracil,FU,Cisplatin,DDP,while,overexpression,enhances,Furthermore,depending,motor,domain,tail,regulates,DDR,induced,by,treatment,In,conclusion,demonstrate,independent,through,controlling

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