Knockdown of DLGAP5 suppresses cell proliferation, induces G<sub>2</sub>/M phase arrest and apoptosis in ovarian cancer

Zhang, Huijun; Liu, Yuan; Tang, Shengchun; Qin, Xuzhen; Li, Lin; Zhou, Jiarong; Zhang, Jing; Liu, Bo

doi:10.3892/etm.2021.10680

Cited by 19 publications

(15 citation statements)

References 43 publications

(41 reference statements)

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“…Additionally, the hub genes of NCAPG, CCNB1, and DLGAP5 were overexpressed in subtype1 in the training data set (see Figure 5) and subtype 2 in the validation data set (see Figure S5). Consistent with the literature, we found that DLGAP5 overexpression in tumor patients was associated with a poor prognosis (20,21). The clinical data of the LUAD patients were also analyzed.…”

Section: Validation Of Subtypes and The Correlation Between Subtypes ...supporting

confidence: 79%

Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling—a bioinformatic analysis

Wang¹,

Liang²,

Guo³

et al. 2022

Ann Transl Med

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Background: Molecular typing based on deoxyribonucleic acid (DNA) methylation and gene expression can extend understandings of the molecular mechanisms involved in lung adenocarcinoma (LUAD) and enhance current diagnostic, treatment, and prognosis prediction approaches.Methods: Gene expression and DNA methylation data sets of LUAD were obtained from The Cancer Genome Atlas (TCGA), and the differential gene and methylation expression levels were analyzed.Results: We successfully divided the LUAD samples into 2 clinically relevant subtypes with significantly different survival times and tumor stages according to the transcriptome and methylation data. We found significant differences in the survival status, age, gender, tumor stage, node stage, and clinical stage between the 2 subtypes. The hub genes identified in the subnetworks, including NCAPG, CCNB1, DLGAP5, HLA-DQA1, HLA-DPA1, HLA-DPB1, SFTP, SCGBA1A, and SFTPD, were correlated with the cell cycle and immune system. The Gene Ontology annotation of the hub genes showed that the biological processes included organelle fission mitotic nuclear division, and sister chromatid segregation. The cellular components included chromosomal region, spindle, and kinetochore. The molecular functions included tubulin-binding, microtubule-binding, and DNA replication origin binding. The Kyoto Encyclopedia of Genes and Genomes signaling pathways related to the hub genes mainly included the cell cycle, human T-cell leukemia virus (type 1) infection, inflammatory bowel disease, and the intestinal immune network for immunoglobulin A production. The clinical stage difference was also confirmed in the validation group using the GSE32863 data set.Conclusions: Our findings extend understandings of the pathogenesis of LUAD and can be used to improve current diagnosis, treatment, and prognosis prediction strategies.

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Section: Validation Of Subtypes and The Correlation Between Subtypes ...supporting

confidence: 79%

Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling—a bioinformatic analysis

Wang¹,

Liang²,

Guo³

et al. 2022

Ann Transl Med

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“…However, tumor cells exploit the property that DLGAP5 can regulate the cell cycle to promote proliferation. For instance, downregulation of DLGAP5 expression suppressed the proliferation and induced cell cycle arrest of ovarian and breast cancer cells [ 19 , 20 ]. According to the results of our RNA sequencing and enrichment analysis, DLGAP5-related genes were located in the chromosomal and centromeric regions and were primarily engaged in the regulation of the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

High Expression of DLGAP5 Indicates Poor Prognosis and Immunotherapy in Lung Adenocarcinoma and Promotes Proliferation through Regulation of the Cell Cycle

2023

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Background. Lung adenocarcinoma (LUAD) is one of the most common types of cancer in the respiratory system, with a high mortality and recurrence rate. The role of disc large-associated protein 5 (DLGAP5) in LUAD progression and tumor microenvironment (TME) remains unclear. This study is aimed at revealing the functional role of DLGAP5 in LUAD based on bioinformatics analysis and experimental validation. Methods. Differential expression analysis, protein-protein interaction (PPI) network, and Cox regression analysis were applied to screen potential prognostic biomarkers. The mRNA and protein levels of DLGAP5 were analyzed using The Cancer Genome Atlas (TCGA) and the Human Protein Atlas (HPA) databases. The CCK-8 and colony formation assays were performed to assess the effect of DLGAP5 on cell proliferation. RNA sequencing (RNA-seq) and enrichment analyses were utilized to explore the biological functions of DLGAP5. Furthermore, flow cytometry was used to explore the role of DLGAP5 on the cell cycle. The ssGSEA algorithm in the R package “GSVA” was applied to quantify immune infiltrating cells, and the tumor immune dysfunction and exclusion (TIDE) algorithm was used to predict the efficacy of immunotherapy. Moreover, analyses using the cBioPortal and MethSurv databases were performed to evaluate the mutation and methylation of DLGAP5, respectively. Finally, the prognostic value of DLGAP5 was estimated using the TCGA and the Gene Expression Omnibus (GEO) databases. The nomogram model was constructed using the TCGA-LUAD cohort and evaluated by adopting calibration curves, time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results. DLGAP5 mRNA and protein abundance were significantly elevated in LUAD, and knockdown of DLGAP5 remarkably suppressed lung cancer cell proliferation through induction of cell cycle G1 arrest. In addition, DLGAP5 expression was positively correlated with Th2 cells and negatively correlated with B cells, T follicular helper cells, and mast cells. LUAD patients with high DLGAP5 expression may be resistant to immunotherapy. Hypermethylation levels of the cg23678254 site of DLGAP5 or its enhanced expression were unfavorable for the survival of LUAD patients. Meanwhile, DLGAP5 expression was associated with TNM stages, tumor status, and therapy outcome. Notably, the prognostic model constructed based on DLGAP5 expression exhibited great predictive capability, which was promising for clinical applications. Conclusion. DLGAP5 promotes lung cancer cell proliferation through regulation of the cell cycle and is associated with multiple immune infiltrating cells. Furthermore, DLGAP5 predicts poor prognosis and response to immunotherapy in lung adenocarcinoma.

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“…reported that silencing the expression of DLGAP5 suppressed cell growth significantly and colony formation in hepatocellular carcinoma cells in vitro. Zhang et al also reported that knockdown of DLGAP5 suppressed cell proliferation, induced G2/M phase arrest and apoptosis in ovarian cancer (Zhang et al, 2021). However, the functional experiment of DLGAP5 in BC was not observed.…”

Section: Discussionmentioning

confidence: 98%

NEAT1/MALAT1/XIST/PKD--Hsa-Mir-101-3p--DLGAP5 Axis as a Novel Diagnostic and Prognostic Biomarker Associated With Immune Cell Infiltration in Bladder Cancer

Rao

Cao

et al. 2022

Front. Genet.

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Background: The clinical value of the biomarkers of bladder cancer (BC) is limited due to their low sensitivity or specificity. As a biomarker, DLG associated protein 5 (DLGAP5) is a potential cell cycle regulator in cancer cell carcinogenesis. However, its functional part in BC remains unclear. Therefore, this study aims to identify DLGAP5 expression in BC and its potential diagnostic and prognostic values. Eventually, it predicts the possible RNA regulatory pathways of BC.Methods: Data on DLGAP5 expression levels in BC and normal bladder tissues were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The receiver operating characteristic (ROC), Kaplan–Meier survival curves, and the univariate and multivariate Cox regression analysis determined the diagnostic and prognostic values of DLGAP5 in BC patients. Finally, the StarBase predicted the target RNAs and constructed networks using Cytoscape.Results: DLGAP5 expression was significantly upregulated in BC tissue, verified by the TCGA (p < 0.001), GSE3167, GSE7476, and GSE65635 datasets (p < 0.01). BC patients with increased DLGAP5 had poor overall survival (OS) (p = 0.01), disease specific survival (DSS) (p = 0.006) and progress free interval (DFI) (p = 0.007). The area under the ROC curve (AUC) was 0.913. The multivariate Cox analysis identified that lymphovascular invasion (p = 0.007) and DLGAP5 (p = 0.002) were independent prognostic factors.Conclusion: Increased DLGAP5 expression was closely associated with a poor prognosis in BC patients. In this case, DLGAP5 might be a diagnostic and prognostic biomarker for BC. DLGAP5 expression might be regulated by NEAT1/MALAT1/XIST/PKD--Hsa-mir-101-3p pathways.

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Knockdown of DLGAP5 suppresses cell proliferation, induces G₂/M phase arrest and apoptosis in ovarian cancer

Cited by 19 publications

References 43 publications

Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling—a bioinformatic analysis

Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling—a bioinformatic analysis

High Expression of DLGAP5 Indicates Poor Prognosis and Immunotherapy in Lung Adenocarcinoma and Promotes Proliferation through Regulation of the Cell Cycle

NEAT1/MALAT1/XIST/PKD--Hsa-Mir-101-3p--DLGAP5 Axis as a Novel Diagnostic and Prognostic Biomarker Associated With Immune Cell Infiltration in Bladder Cancer

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Knockdown of DLGAP5 suppresses cell proliferation, induces G2/M phase arrest and apoptosis in ovarian cancer

Cited by 19 publications

References 43 publications

Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling—a bioinformatic analysis

Identification of molecular subtypes in lung adenocarcinoma based on DNA methylation and gene expression profiling—a bioinformatic analysis

High Expression of DLGAP5 Indicates Poor Prognosis and Immunotherapy in Lung Adenocarcinoma and Promotes Proliferation through Regulation of the Cell Cycle

NEAT1/MALAT1/XIST/PKD--Hsa-Mir-101-3p--DLGAP5 Axis as a Novel Diagnostic and Prognostic Biomarker Associated With Immune Cell Infiltration in Bladder Cancer

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Knockdown of DLGAP5 suppresses cell proliferation, induces G₂/M phase arrest and apoptosis in ovarian cancer