FOXP3 targets KIF5A to increase lactate production and promote docetaxel resistance in lung adenocarcinoma  

作　　者：Liangliang Dong Chan Feng Wenwen Cheng Aihua Huang Kejing Ying 

机构地区：[1]Department of Respiratory and Critical Care Medicine,Regional Medical Center for National Institute of Respiratory Diseases,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310020,China [2]Department of Education Office,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310020,China [3]Department of Pathology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310020,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第7期1011-1021,共11页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Medical and Health Program of Zhejiang Province,China(No.2018251155);the National Science Foundation of Zhejiang Province(No.LTGY23H010006).

摘　　要：A prominent cause of cancer-related fatalities with a poor prognosis is lung adenocarcinoma(LUAD).KIF5A,a crucial member of the kinesin superfamily,is linked to drug resistance in malignancies.This work aims to investigate the mechanism of KIF5A in docetaxel(DTX)resistance in LUAD cells.The results of bioinformatics analysis,qRT-PCR and western blot analysis show that KIF5A,which is involved in the glycolysis pathway,is highly expressed in LUAD and is positively correlated with glycolysis-related genes.We further verify that silencing of KIF5A inhibits DTX resistance,glycolysis,and lactate production in LUAD cells via cell counting kit-8(CCK-8),flow cytometry,Seahorse XFe 96,lactate,and glucose assays.Mechanistically,KIF5A promotes DTX resistance in LUAD,and this effect is attenuated upon the addition of an LDHA inhibitor.Chromatin immunoprecipitation and dual-luciferase reporter assays reveal that FOXP3 transcriptionally activates KIF5A.Knockdown of FOXP3 reduces lactate production and enhances DTX sensitivity in LUAD,which is restored upon simultaneous overexpression of KIF5A.Our findings reveal that FOXP3 increases DTX resistance in LUAD cells by enhancing lactate production through the upregulation of KIF5A level.In conclusion,our study provides a novel treatment target for improving chemosensitivity in LUAD.

关 键 词：KIF5A FOXP3 lung adenocarcinoma LACTATE DOCETAXEL 

分 类 号：R734.2[医药卫生—肿瘤]