Current cancer drug targets最新文献

{"title":"PLCG2, A Regulator of Lung Adenocarcinoma Proliferation and Migration Associated with Immune Infiltration.","authors":"Shuhui Chen, Chenkang Zhou, Jieying Dai, Qingqing Xu, Yuxin Chen, Zhaoting Hu, Yumin Wang, Caihong Wang","doi":"10.2174/0115680096307100240801095132","DOIUrl":"https://doi.org/10.2174/0115680096307100240801095132","url":null,"abstract":"<p><strong>Background: </strong>Results from the TCGA database showed that phosphatidylinositol-specific phospholipase Cγ2 (PLCG2) expression level in Lung Adenocarcinoma (LUAD) was notably decreased compared to adjacent tissues, so we unveiled its role of LUAD.</p><p><strong>Objective: </strong>This study aims to explore the expression and clinical significance of Phosphatidyl-inositol-specific phospholipase Cγ2 (PLCG2) in lung adenocarcinoma (LUAD) cells and its role in cell proliferation and metastasis.</p><p><strong>Methods: </strong>Differential PLCG2 mRNA and protein levels between LUAD tissues and adjacent tissues were analyzed from the TCGA database, TIMER, and UALCAN database. Differentially expressed genes were screened for patients in the high and low PLCG2 mRNA expression groups by the R package as well as GSEA. The expression level of PLCG2 in LUAD cells was detected using qRT-PCR and CCK8, clone formation, Transwell, and Western blot assays.</p><p><strong>Results: </strong>PLCG2 was lowly expressed in LUAD and did not significantly correlate with the prognosis of LUAD. PLCG2 expression levels varied significantly in terms of patients' gender, age, T, N, and pathological stage. GO/KEGG enrichment analysis showed that co-expression of PLCG2 was mainly associated with the immune response- regulating cell-surface receptors, and so on. GSEA analysis showed enrichment pathways of PLCG2-related differential gees were primarily associated with the olfactory transduction pathway, ribosome, etc. R software analysis revealed a significant correlation between PLCG2 expression and six types of immune-infiltrat-ing cells, positively correlated with immune checkpoint-related genes and negatively regulated by tumor mutational load. Overexpressing PLCG2 showed reduced LUAD cell proliferation, clone formation, cell migration and invasion, and epithelial-mesenchymal transition-associated proteins, compared with the control group.</p><p><strong>Conclusion: </strong>PLCG2 is lowly expressed in LUAD tissues and is involved in immune infiltration of LUAD, inhibiting LUAD cell proliferation and metastasis.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Deoxyguanosine Kinase Induces 5-Fluorouracil Chemotherapy Sensitivity through Autophagy.","authors":"Lu Dong, Sifan Liu, Wenjing Sun, Siying Liu, Nan Zhang, Shutian Zhang","doi":"10.2174/0115680096337375240801080008","DOIUrl":"https://doi.org/10.2174/0115680096337375240801080008","url":null,"abstract":"<p><strong>Aims: </strong>The purpose of this study was to investigate the role of DGUOK in the pro-gression of colorectal cancer (CRC) and its impact on the sensitivity of CRC cells to 5-FU treatment.</p><p><strong>Methods: </strong>We conducted bioinformatics analysis and qRT-PCR to evaluate DGUOK expression in CRC tissues/cells. Cell viability of CRC cells treated with 5-FU was assessed using CCK-8 and colony formation assays. Autophagy levels were determined through immunofluorescence assays and Western blot analysis. Additionally, the influence of p-p38 on autophagy was inves-tigated via Western blotting. A rescue assay was performed to confirm whether DGUOK/p38 affects 5-FU sensitivity in CRC cells through autophagy.</p><p><strong>Results: </strong>Our findings indicate that DGUOK is upregulated in CRC tissues compared to normal tissues, correlating with increased cell proliferation and migration. Functionally, inhibition of DGUOK enhances autophagy, thereby decreasing the sensitivity of CRC cells to 5-FU. This ef-fect is partly mediated by DGUOK's impact on the mitogen-activated protein kinase (MAPK) pathway, specifically promoting the phosphorylation of p38 MAPK, a crucial regulator in au-tophagy pathways.</p><p><strong>Conclusion: </strong>These results suggest that DGUOK could serve as a novel marker for predicting the efficacy of 5-FU in CRC treatment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Bioinformatic Strategy for Investigating the Mechanism of Hispolon in the Treatment of Triple-Negative Breast Cancer Combined with In vitro Experiments.","authors":"Junfeng Li, Jingfei Bao, Lichao Wu, Tengfei Sun, Junhui Zhao, Fei Luo, Fangfang Tao, Wenhong Liu","doi":"10.2174/0115680096313623240801070716","DOIUrl":"https://doi.org/10.2174/0115680096313623240801070716","url":null,"abstract":"<p><strong>Background: </strong>Hispolon, a phenolic compound isolated from the medicinal yellow fungal mulberry, exhibits a strong anti-triple-negative breast cancer (TNBC) effect. However, the antitumor mechanisms of Hispolon have not been fully explored.</p><p><strong>Objective: </strong>In this study, we systematically investigated the mechanism of Hispolon against TNBC based on bioinformatics and in vitro experiments.</p><p><strong>Methods: </strong>The Hispolon-related targets were first collected from the SwissTarget database. Differential Expression Genes (DEG) were screened between TNBC and normal breast tissue using the Gene Expression Comprehensive (GEO) dataset. The overlapping targets between Hispolon and DEG were analyzed by plotting Venn maps. Protein-protein interaction (PPI) network was constructed to analyze the interactions among these targets. The focus was on mining the core targets of anti-TNBC effects of Hispolon via the Cytohubba and MCODE plugin of Cytoscape 3.7.2 software. We performed survival analysis on these core targets to screen the best-matched targets, including EGFR, KIT, and PLAU. This correlated strongly with our validation of Hispolon by molecular docking. In addition, Gene Ontology (GO) anal-ysis and KEGG pathway analysis were performed using R software (ClusterProfiler package). Finally, in vitro experiments were performed to assess the accuracy of predicted target genes.</p><p><strong>Results: </strong>The ADME results suggested that Hispolon has great potential to develop into a drug. Twenty overlapping targets were screened by matching the 107 targets of Hispolon to the 2,013 targets of TNBC DEG. Seven core targets of Hispolon against TNBC were initially identified, including EGFR, IGFBP3, MMP9, MMP2, MMP1, PLAU, and KIT. GO enrich-ment analysis demonstrated that the biological process of Hispolon acting on TNBC mainly involves lymphocyte activation in immune response and phosphatidylinositol-mediated signal-ing. Additionally, the relaxin signaling pathway, estrogen signaling pathway, proteoglycans in cancer, and others might be the key pathways of Hispolon against TNBC. Furthermore, Hispo-lon inhibited the proliferation of MDA-MB-231 cells in a concentration-dependent manner and regulated the RNA and protein expression of the core targets EGFR, PLAU, and KIT for the treatment of TNBC.</p><p><strong>Conclusion: </strong>In this study, the polygenic pharmacological mechanism of action of Hispolon against TNBC was explored through network pharmacology and in vitro experiments, provid-ing a new insight into the mechanism of TCM monomer against TNBC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal CircRNAs: A Future Star in Colorectal Cancer.","authors":"Yuanzhi Zhou, Chengyan Wei, Yuqi Xu, Jingjing Wang, Chunwei Zhang, Yong Jin","doi":"10.2174/0115680096323472240710101854","DOIUrl":"https://doi.org/10.2174/0115680096323472240710101854","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is currently the third most common malignancy world-wide, with an increasing mortality rate and treatment resistance. Due to the lack of effective biomarkers and therapeutic targets, the early diagnosis and treatment of colorectal cancer re-main suboptimal. Circular RNAs (circRNAs) are a novel class of non-coding RNAs with co-valent closed-loop structures that are well stabilized and conserved and are involved in multi-ple pathological conditions in humans. CircRNAs have been identified to be enriched and sta-ble in exosomes. In addition, there is growing proof that exosomal circRNAs that have been identified as oncogenes or tumor suppressors regulate CRC growth, migration, and sensitivity to radiotherapy and chemotherapy. Exosomal circRNAs represent promising candidates as di-agnostic biomarkers and anti-tumor targets. In this article, we explore recent studies on exo-somal circRNAs in CRC and describe their biological functions in colorectal cancer develop-ment, illustrating their potential as biomarkers and targeted therapeutic capabilities.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on Novel Pathways in Cancer Treatment: Clinical Applications and Future Prospects.","authors":"A S Shifana, Mohammad Adnan, Akash Gupta, Ajazuddin, Parag Jain","doi":"10.2174/0115680096312603240709112520","DOIUrl":"https://doi.org/10.2174/0115680096312603240709112520","url":null,"abstract":"<p><p>Cancer is a global health issue that requires ongoing therapeutic advances. This review provides an overview of recent treatment strategies focusing on novel pathways in cancer therapy. Emerging research has unveiled promising targets that go beyond traditional modalities, offering new avenues for precision medicine and improved patient outcomes. One key area of innovation lies in targeted therapies directed at specific molecular pathways implicated in cancer progression. The identification of novel biomarkers has paved the way for the development of precision medicines tailored to individual patient profiles. Immunotherapy has also revolutionised cancer treatment by using the immune system to identify and remove cancer cells. Moreover, advancements in epigenetic therapies and RNA-based interventions demonstrate unprecedented potential in modulating gene expression and disrupting cancer-specific signalling pathways. We have discussed the pathophysiology of cancer, different immune checkpoint inhibitors, and targeted therapies in signalling therapies. The epigenetic modulators, such as Histone deacetylase (HDACs) inhibitors and DNA methyltransferase (DNMT) inhibitors, were studied. Recent breakthroughs in cancer immunotherapy treatment (CAR-T) cell therapy showcase the potential to enhance the immune response against various cancers; thus, related information was incorporated. Further, RNA-based therapies like RNA interference and mRNA-based vaccines and therapies, combination therapies, and novel therapies were discussed in the present article.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology-Based Virtual Screening of Chemical Constituents from Vitexnegundo Linn's Discovered Novel Molecular Targets for Breast Cancer Treatment.","authors":"Rajesh Basnet, Buddha Bahadur Basnet, Obed Boadi Amissah, Rongqi Huang, Yirong Sun, Jean de Dieu Habimana, Zhiyuan Li","doi":"10.2174/0115680096316247240715064729","DOIUrl":"10.2174/0115680096316247240715064729","url":null,"abstract":"<p><strong>Background: </strong>The Chinese chaste tree Vitexnegundo (VN) is a popular herb in South and Southeast Asia that has several health benefits, including the ability to inhibit tumor growth and induce apoptosis in multiple tumors. Literature revealed scanty research on breast cancer, with little focus on the molecular mechanism of the disease and an emphasis on targets, biological networks, and active components. Exploring natural compounds as possible therapeutic options is an old but still promising approach for drug discovery and development. This study used a thorough computational and statistical method to screen potential drug candidates.</p><p><strong>Methods: </strong>The active ingredients and targets of VN were identified using SwissADME, SwissTargetPrediction, STITCH, IMPPAT database, KNapSAcK database, and literature. The OMIM and GeneCards databases were searched for possible targets related to breast cancer. The PASS online server was used to check the probability of active metabolite (Pa) against breast cancer. To build protein-protein interactions (PPI) networking, the intersection of disease and drug targets was uploaded to the STITCH database. Cytoscape software was used to analyze the topology parameters of networking to identify hub targets. Gene Ontology (GO) was analyzed using Metascape and ShinyGO, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed using the David database and SR plot, and the site of expression and protein domain were studied using FunRich. We employed AutoDockvina, Discovery Studio, and UCSF ChimeraX software and auxiliary tools for molecular docking and analysis. Zincpharmer was used for pharmacophore mapping. ADMET analysis was conducted using ADMETsar, Swiss ADME, ADMETLab servers, and mypresto using GROMACS for molecular dynamics simulation (MDS).</p><p><strong>Results: </strong>A total of 65 targets and 21 active ingredients were identified. Further investigation was conducted on 20 hub targets selected through PPI networking construction. The enrichment analysis results indicated that the key factors were P, amyloid-beta response, cellular response to amyloid- beta, Pos. reg. of G2/M transition of the mitotic cell cycle, and response to a toxic substance. The molecular docking, pharmacophore mapping, and MD simulation results indicated that apigenin, kaempferol, and luteolin positively interacted with CDK1 and CDK6 proteins.</p><p><strong>Conclusion: </strong>This study is the first to use network pharmacology, molecular docking, pharmacophore mapping, and MD simulation to identify the active ingredients, molecular targets, and critical biological pathways responsible for VN anti-breast cancer. The study provides a theoretical basis for further research in this area.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA DERCNC in Hepatocellular Carcinoma with Cirrhosis Aggravates Tumor Proliferation by Targeting SOX9.","authors":"Yun-Bing Wang, Haitham Salameen, Yi-Yu Hu, Shi-Ji Zhou, Jun-Hua Gong","doi":"10.2174/0115680096310229240626102449","DOIUrl":"https://doi.org/10.2174/0115680096310229240626102449","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to understand the role of cirrhosis in promoting hepatocellular carcinoma (HCC) progression by analyzing the differential expression of long noncoding RNAs (lncRNAs) between cirrhotic hepatocellular carcinoma (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC).</p><p><strong>Methods: </strong>A transcriptional profile array was used to identify differentially expressed lncRNAs. Subsequently, a specific lncRNA was selected to evaluate the clinical significance, potential functions, regulatory targets, and pathways through both in vitro and in vivo experiments.</p><p><strong>Results: </strong>The study identified a lncRNA, which we termed DERCNC, an acronym for Differentially Expressed RNA between Cirrhotic and Non-Cirrhotic HCC. DERCNC was significantly more highly expressed in CHCC than in NCHCC. Clinically, elevated levels of DERCNC expression were positively correlated with both the cirrhotic state and tumor stage and inversely correlated with tumor differentiation. Furthermore, high expression of DERCNC was associated with a poor prognosis for patients. Conditioned medium from the hepatic stellate cell (LX2) was found to enhance DERCNC expression, SOX9 expression, and tumor proliferation. Overexpression of DERCNC similarly promoted tumor proliferation and increased SOX9 levels. Conversely, DERCNC silencing resulted in the opposite effects. Moreover, the pro-proliferative function of DERCNC was reversible through the modulation of SOX9 expression. Further mechanistic studies revealed that DERCNC upregulated SOX9 by increasing the enrichment of H3K27ac modifications near the SOX9 promoter.</p><p><strong>Conclusion: </strong>In conclusion, DERCNC expression in CHCC has significant clinical implications and can aggravate tumor proliferation by targeting SOX9. This represents a novel mechanism by which cirrhosis promotes tumor progression.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Long Noncoding RNA PANDAR as a Prognostic and Diagnostic Biomarker in Panceratic Cancer ‏‏.","authors":"Shima Mehrabadi, Samaneh Mollazadeh, Amir Avan","doi":"10.2174/0115680096300768240604045809","DOIUrl":"https://doi.org/10.2174/0115680096300768240604045809","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is a lethal complication in the world, affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Most PC patients are confronted with locally metastatic or advanced diseases in the asymptomatic phase, and about 80% have late diagnosis with metastasis. Recently, long noncoding RNAs (lncRNAs) have drawn attention as a novel biological regulation layer. They take part in the regulation of mRNA and can be used as a prognostic factor or drug target. Based on their functions as regulators of PC initiation and progress, the lncRNAs can be categorized as tumor suppressors or oncogenic. They can be considered as a target for finding new biomarkers for prognosis, diagnosis, monitoring, and treating drug response in PC. Therefore, the present study summarizes the lncRNAs role in PC and the probable strategies to deal with their expression and controlling tumorigenesis and detection of the prognosis of PC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Metastasis: From Cell Death to Fusion in Cancer Progression.","authors":"Evgeniya V Kaigorodova, Alexey V Kozik, Maxim Y Grishchenko","doi":"10.2174/0115680096308596240620055942","DOIUrl":"https://doi.org/10.2174/0115680096308596240620055942","url":null,"abstract":"<p><p>Metastasis is one of the key concepts in modern oncology, which connects the movement of cancer cells in the body with changes in their characteristics and functions. The review examines the main aspects of metastasis, including theories, facts and discoveries that help to better understand this phenomenon and develop new approaches to its treatment. In this article, we also proposed the theory of cell fusion with the formation of hybrid cells as one of the factors of metastasis. We believe that the fusion of tumor cells with other types of motile cells (leukocytes and bone marrow progenitor cells) may represent an additional mechanism of tumor spread. Cells of bone marrow origin, including cells of the myeloid and macrophage lineages, are the best candidates for heterotypic fusion in regenerative conditions. Events such as cell fusion may play a role in tumor dedifferentiation and progression. We presented a number of arguments and data from our own research that speak in favor of the proposed theory. It should be noted that if the fusion of a normal cell with a tumor cell is one of the possible triggers of tumorigenesis and cancer spread, the mechanisms underlying this process may provide possible new targets for treatment. Therefore, their analysis will expand our arsenal of therapeutic tools by adding completely new targets - cell signaling molecules - and will provide the impetus for reconsidering the tumor microenvironment from a different angle.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GAPVD1 Promotes the Proliferation of Triple-Negative Breast Cancer Cells by Regulating the ERK/MAPK Signaling Pathway.","authors":"Lu Wang, Lifen Zhang, Pei Luo, Zeyu Xia, Shan Shao, Qian Ning, Shanzhi Gu, Xinhan Zhao, Minna Luo","doi":"10.2174/0115680096303983240616191051","DOIUrl":"https://doi.org/10.2174/0115680096303983240616191051","url":null,"abstract":"<p><strong>Background: </strong>Triple-Negative Breast Cancer (TNBC) accounts for 15-20% of all breast cancers and approximately 50% of breast cancer deaths. Chemotherapy remains the mainstay of systemic treatment due to the lack of effective therapy targets. Thus, more studies are urgently needed to identify new therapeutic targets in TNBC patients.</p><p><strong>Methods: </strong>GAPVD1 expression and prognosis value in breast cancer samples were explored in The Cancer Genome Atlas database (TCGA). GAPVD1 knockdown and overexpression TNBC cell lines were constructed. CCK-8 and colony formation assays were performed to detect cell viability. Flow cytometry analysis was performed to detect cell cycle variation. Western blotting was conducted to determine the levels of target genes. Finally, an enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed.</p><p><strong>Results: </strong>GAPVD1 is overexpressed in breast cancer tissues and predicts poor prognosis. In vitro experiments demonstrated that GAPVD1 is correlated with cell proliferation and the cell cycle of TNBC cells. Mechanistically, alteration in GAPVD1 expression was found to be associated with cell cycle-related proteins PCNA, Cyclin A, and the activity of the ERK/MAPK signaling pathway. Consistent with these findings, enrichment analysis of GAPVD1-involving partners and signaling pathways revealed that the cellular biosynthetic process, macromolecule biosynthetic process, and cell cycle signaling are related to GAPVD1. In vivo experiment demonstrated that GAPVD1 inhibition impedes tumor growth and expression of cell cyclerelated proteins.</p><p><strong>Conclusion: </strong>Taken together, our results indicate that GAPVD1 may participate in TNBC cell growth by regulating the cell cycle and ERK/MAPK signaling pathway.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}