Mengjie Wang, David Lukanovic, Fabio Barra, Aoli Lei
{"title":"KIF18A和CDK1联合治疗宫颈癌和子宫内膜癌：基于生物信息学分析和体外实验","authors":"Mengjie Wang, David Lukanovic, Fabio Barra, Aoli Lei","doi":"10.21037/tcr-24-1831","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chromosomal instability (CIN) has been identified as a factor that increases the susceptibility of tumor cells to kinesin family member 18A (KIF18A) inhibitors. Limited research exists on genes that are associated with sensitization to KIF18A inhibitors (KIF18Ais). Our study aimed to identify a gene linked to heightened sensitivity to KIF18Ais in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and uterine corpus endometrial carcinoma (UCEC).</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) and X2K Appyter databases were used to analyze potential kinases associated with <i>KIF18A</i>-related genes in CESC and UCEC. <i>In vitro</i> assessments, such as Cell Counting Kit-8 (CCK-8), transwell, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays, were performed to evaluate the combined effects of KIF18A and cyclin-dependent kinase 1 inhibitors (CDK1is) in CESC and UCEC cell lines.</p><p><strong>Results: </strong>Our findings indicated that the combination of <i>KIF18A</i> with kinases may potentially augment the efficacy of KIF18Ais, given its close involvement in cell cycle and chromosome segregation. Through bioinformatics analysis, we observed a significant up-regulation of CDK1 expression in CESC and UCEC, which exhibited a strong correlation with KIF18A expression. Our hypothesis regarding the potential of CDK1 as a combination therapeutic target for KIF18A was supported by our cell experiments, which demonstrated that inhibition of CDK1 notably increased the sensitivity of CESC and UCEC cells to KIF18Ais. The combined use of CDK1is and KIF18Ais exhibited a synergistic effect in inhibiting cell migration and inducing apoptosis in CESC and UCEC cells.</p><p><strong>Conclusions: </strong>This study provides evidence that targeting both KIF18A and CDK1 exerts synergistic anti-tumor effects in CESC and UCEC via inhibiting cell proliferation and migration and inducing apoptosis, suggesting a promising therapeutic strategy for these cancers.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"13 12","pages":"6880-6894"},"PeriodicalIF":1.5000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730454/pdf/","citationCount":"0","resultStr":"{\"title\":\"KIF18A and CDK1 as combined therapeutic targets in cervical and endometrial carcinomas: based on bioinformatics analysis and <i>in vitro</i> experiments.\",\"authors\":\"Mengjie Wang, David Lukanovic, Fabio Barra, Aoli Lei\",\"doi\":\"10.21037/tcr-24-1831\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chromosomal instability (CIN) has been identified as a factor that increases the susceptibility of tumor cells to kinesin family member 18A (KIF18A) inhibitors. Limited research exists on genes that are associated with sensitization to KIF18A inhibitors (KIF18Ais). Our study aimed to identify a gene linked to heightened sensitivity to KIF18Ais in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and uterine corpus endometrial carcinoma (UCEC).</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA) and X2K Appyter databases were used to analyze potential kinases associated with <i>KIF18A</i>-related genes in CESC and UCEC. <i>In vitro</i> assessments, such as Cell Counting Kit-8 (CCK-8), transwell, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays, were performed to evaluate the combined effects of KIF18A and cyclin-dependent kinase 1 inhibitors (CDK1is) in CESC and UCEC cell lines.</p><p><strong>Results: </strong>Our findings indicated that the combination of <i>KIF18A</i> with kinases may potentially augment the efficacy of KIF18Ais, given its close involvement in cell cycle and chromosome segregation. Through bioinformatics analysis, we observed a significant up-regulation of CDK1 expression in CESC and UCEC, which exhibited a strong correlation with KIF18A expression. Our hypothesis regarding the potential of CDK1 as a combination therapeutic target for KIF18A was supported by our cell experiments, which demonstrated that inhibition of CDK1 notably increased the sensitivity of CESC and UCEC cells to KIF18Ais. The combined use of CDK1is and KIF18Ais exhibited a synergistic effect in inhibiting cell migration and inducing apoptosis in CESC and UCEC cells.</p><p><strong>Conclusions: </strong>This study provides evidence that targeting both KIF18A and CDK1 exerts synergistic anti-tumor effects in CESC and UCEC via inhibiting cell proliferation and migration and inducing apoptosis, suggesting a promising therapeutic strategy for these cancers.</p>\",\"PeriodicalId\":23216,\"journal\":{\"name\":\"Translational cancer research\",\"volume\":\"13 12\",\"pages\":\"6880-6894\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-12-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730454/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tcr-24-1831\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-1831","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/18 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
KIF18A and CDK1 as combined therapeutic targets in cervical and endometrial carcinomas: based on bioinformatics analysis and in vitro experiments.
Background: Chromosomal instability (CIN) has been identified as a factor that increases the susceptibility of tumor cells to kinesin family member 18A (KIF18A) inhibitors. Limited research exists on genes that are associated with sensitization to KIF18A inhibitors (KIF18Ais). Our study aimed to identify a gene linked to heightened sensitivity to KIF18Ais in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and uterine corpus endometrial carcinoma (UCEC).
Methods: The Cancer Genome Atlas (TCGA) and X2K Appyter databases were used to analyze potential kinases associated with KIF18A-related genes in CESC and UCEC. In vitro assessments, such as Cell Counting Kit-8 (CCK-8), transwell, and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays, were performed to evaluate the combined effects of KIF18A and cyclin-dependent kinase 1 inhibitors (CDK1is) in CESC and UCEC cell lines.
Results: Our findings indicated that the combination of KIF18A with kinases may potentially augment the efficacy of KIF18Ais, given its close involvement in cell cycle and chromosome segregation. Through bioinformatics analysis, we observed a significant up-regulation of CDK1 expression in CESC and UCEC, which exhibited a strong correlation with KIF18A expression. Our hypothesis regarding the potential of CDK1 as a combination therapeutic target for KIF18A was supported by our cell experiments, which demonstrated that inhibition of CDK1 notably increased the sensitivity of CESC and UCEC cells to KIF18Ais. The combined use of CDK1is and KIF18Ais exhibited a synergistic effect in inhibiting cell migration and inducing apoptosis in CESC and UCEC cells.
Conclusions: This study provides evidence that targeting both KIF18A and CDK1 exerts synergistic anti-tumor effects in CESC and UCEC via inhibiting cell proliferation and migration and inducing apoptosis, suggesting a promising therapeutic strategy for these cancers.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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