Kinesin Family Member-18A (KIF18A) Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma

作者全名："Ren, Jihua; Yao, Xinyan; Yang, Minli; Cheng, Shengtao; Wu, Daiqing; Xu, Kexin; Li, Ranran; Zhang, Han; Zhang, Dapeng"

作者地址："[Ren, Jihua; Yao, Xinyan; Yang, Minli; Cheng, Shengtao; Wu, Daiqing; Xu, Kexin; Li, Ranran; Zhang, Han; Zhang, Dapeng] Chongqing Med Univ, Key Lab Mol Biol Infect Dis Designated Chinese, Minist Educ, Chongqing 400016, Peoples R China; [Zhang, Dapeng] Room 706,Chongyi Bldg,1 Yixue Yuan Rd, Chongqing 400016, Peoples R China"

通信作者："Zhang, DP (通讯作者)，Chongqing Med Univ, Key Lab Mol Biol Infect Dis Designated Chinese, Minist Educ, Chongqing 400016, Peoples R China.; Zhang, DP (通讯作者)，Room 706,Chongyi Bldg,1 Yixue Yuan Rd, Chongqing 400016, Peoples R China."

来源：DIGESTIVE DISEASES AND SCIENCES

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001176976200004

JCR分区：Q2

影响因子：2.5

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Hepatocellular carcinoma; KIF18A; Proliferation; Metastasis; SMAD2/3

摘要："Background & AimsKinesin family member 18A (KIF18A) is notable for its aberrant expression across various cancer types and its pivotal role is driving cancer progression. In this study, we aim to investigate the intricate molecular mechanisms underlying the impact of KIF18A on the progression of HCC.MethodsWestern blotting assays, a quantitative real-time PCR and immunohistochemical analyses were performed to quantitatively assess KIF18A expression in HCC tissues. We then performed genetic manipulations within HCC cells by silencing endogenous KIF18A using short hairpin RNA (shRNA) and introducing exogenous plasmids to overexpress KIF18A. We monitored cell progression, analyzed cell cycle and cell apoptosis and assessed cell migration and invasion both in vitro and in vivo. Moreover, we conducted RNA-sequencing to explore KIF18A-related signaling pathways utilizing Reactome and KEGG enrichment methods and validated these critical mediators in these pathways.ResultsAnalysis of the TCGA-LIHC database revealed pronounced overexpression of KIF18A in HCC tissues, the finding was subsequently confirmed through the analysis of clinical samples obtained from HCC patients. Notably, silencing KIF18A in cells led to an obvious inhibition of cell proliferation, migration and invasion in vitro. Furthermore, in subcutaneous and orthotopic xenograft models, suppression of KIF18A sgnificantly redudce tumor weight and the number of lung metastatic nodules. Mechanistically, KIF18A appears to facilitate cell proliferation by upregulating MAD2 and CDK1/CyclinB1 expression levels, with the activation of SMAD2/3 signaling contributing to KIF18A-driven metastasis.ConclusionOur study elucidates the molecular mechanism by which KIF18A mediates proliferation and metastasis in HCC cells, offering new insights into potential therapeutic targets."

基金机构：Chongqing Natural Science Foundation

基金资助正文：No Statement Available