<scp>DLGAP5</scp> knockdown inactivates the Wnt/β‐catenin signal to repress endometrial cancer cell malignant activities

Chen, Ruipu; Liu, Jing; Hu, Jun; Li, Chunxia; Liu, Yanhua; Pan, Weiwei

doi:10.1002/tox.23720

Cited by 3 publications

(4 citation statements)

References 55 publications

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“…Our results indicate that the deficiency of KIF15 could suppress the EMT process of EC cells, while down‐regulate the self‐renewal ability and the expression of stemness marker molecules of EC cells. It has been reported that Wnt/β‐catenin signaling plays a key role in the malignant proliferation of endometrial cancer cells 39,40 . We also found that KIF15 can affect the dryness of endometrial cancer cells through the Wnt/β‐catenin pathway.…”

Section: Discussionsupporting

confidence: 57%

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KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

Huang

Sun

Diao

et al. 2023

Environmental Toxicology

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Endometrial cancer (EC) is one of the most common cancers among women, while the incidence of EC is rising. Many studies have found that Kinesin family member 15 (KIF15) is highly expressed in a series of cancers, but the role of KIF15 in EC is unclear. We detected the expression level of KIF15 in a microarray of EC tissues by immunohistochemical staining (IHC), and analyzed the correlation between the expression level of KIF15 and the pathological characteristics of patients. After inhibit the expression of KIF15 in EC cells with lentivirus, cell proliferation and apoptosis were detected respectively by CCK8 assay, flow cytometry and tunnel assay. Transwell assay and wound healing assay were used to examine the migration ability and invasion ability of EC cells. Spheroid formation assay was used to evaluate cell self‐renewal ability. In vivo tumor xenograft model was used for validation. The expressions of epithelial‐mesenchymal transition, cancer stem cells, and Wnt/β‐catenin signaling molecules were detected by Western blotting. The results showed that the expression of KIF15 in EC tissues was higher than that in normal endometrial tissues, while the expression level of KIF15 in EC was positively correlated with the pathological grade of the tumor. The down‐regulation of KIF15 reduced the proliferation, colony formation, invasion, migration and self‐renewal ability of EC cells, while promoted cell apoptosis. Knockdown of KIF15 inactivates the Wnt/β‐catenin signaling of EC cells, inhibitors of Wnt signaling can counteract the enhanced self‐renewal ability caused by KIF15 overexpression. Therefore, KIF15 may be a new potential target for diagnosis and treatment of EC.

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Section: Discussionsupporting

confidence: 57%

“…that Wnt/β-catenin signaling plays a key role in the malignant proliferation of endometrial cancer cells. 39,40 We also found that KIF15 can affect the dryness of endometrial cancer cells through the Wnt/βcatenin pathway. Some studies believe that CSCs, as downstream factors, are regulated by EMT.…”

Section: Discussionmentioning

confidence: 67%

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

Huang

Sun

Diao

et al. 2023

Environmental Toxicology

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“…There is evidence that DLGAP5 contributes to tumorigenesis and progression of numerous cancer types, for example, bladder cancer [ 34 ], endometrial cancer [ 35 ], ovarian cancer [ 36 ] and lung cancer [ 37 , 38 ]. In our current study, we conducted bioinformatics, network pharmacology analysis and experimental study to gain a more comprehensive understanding of the potential functions and regulatory mechanisms of DLGAP5 in LUAD.…”

Section: Discussionmentioning

confidence: 99%

DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target

Chen,

Zhang,

Wang

et al. 2024

J Transl Med

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Background Human discs large-associated protein 5 (DLGAP5) is reported to play a pivotal role in regulating the cell cycle and implicate in tumorigenesis and progression of various cancers. Our current research endeavored to explore the prognostic value, immune implication, biological function and targeting strategy of DLGAP5 in LUAD through approaches including bioinformatics, network pharmacology analysis and experimental study. Methods Multiple databases, including TCGA, GEO, CPTAC and Human Protein Atlas, were utilized to explore the expression and clinical significance of DLGAP5 in LUAD. The genetic alterations of DLGAP5 were assessed through cBioPortal and COSMIC databases. The relationship between DLGAP5 expression and genetic abnormalities of driver genes in LUAD was analyzed through TIMER2.0 database. CancerSEA database was utilized to explore the function of DLGAP5 in 14 different states in LUAD at single-cell resolution. GDSC database was utilized to analyze the impact of DLGAP5 on IC50 of frequently-used anti-LUAD drugs. CIBERSORT method and TIMER2.0 database was utilized to explore the relationship between DLGAP5 and tumor immune infiltration. Network pharmacology was applied to screen potential DLGAP5 inhibitor. In vitro and in vivo experiments were utilized to evaluate biological function and downstream targets of DLGAP5, and the effect of screened DLGAP5 inhibitor on LUAD growth. Results High DLGAP5 expression was commonly observed in LUAD and associated with mutation of major driver genes, poor prognosis, high IC50 values of frequently-used anti-LUAD drugs, increasing immune infiltration and elevated immune checkpoint blockade-related genes in LUAD. PLK1 was revealed as a potential DLGAP5 downstream target in LUAD. DLGAP5 overexpression or knockdown significantly promoted or inhibited LUAD cell proliferation and PLK1 expression. PLK1 overexpression well rescued DLGAP5 knockdown-induced cell proliferation inhibition, or vice versa. Furthermore, by virtual screening of an investigational drug library from the DrugBank database, AT9283 was screened and identified as a novel DLGAP5 inhibitor. AT9283 effectively suppressed growth of LUAD cells both in vitro and in vivo. DLGAP5 overexpression significantly reversed AT9283-induced proliferation inhibition. Moreover, AT9283 significantly suppressed DLGAP5 and PLK1 expression, while DLGAP5 overexpression significantly reversed AT9283-induced PLK1 suppression. Conclusion Our research has demonstrated that DLGAP5 is upregulated in LUAD and exhibits a strong correlation with unfavorable prognosis. Furthermore, DLGAP5 assumes a significant function in the regulation of tumor immunity and treatment outcome of immune checkpoint inhibitors. Of note, we found that DLGAP5 promotes cell proliferation of LUAD via upregulating PLK1. Targeting DLGAP5 by AT9283, our newly identified DLGAP5 inhibitor, suppresses LUAD growth. DLGAP5 may become a promising prognostic biomarker and therapeutic target for patients with LUAD.

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“…Inhibition of CDK1 activity has been shown to induce cell cycle arrest, making it a promising target for anticancer therapy [12,13]. DLGAP5, a member of the DLGAP family of proteins, has been implicated in the regulation of cell adhesion and cytoskeletal dynamics, processes that are often disrupted in cancer cells [14,15]. However, the precise role of CDK1 and DLGAP5in HCC progression remains poorly understood, making it an attractive target for further investigation.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatics Analysis Identified a Crucial Role of Tumor Immune Cell Infiltration in Hepatocellular Carcinoma

Li,

Liu,

Zhang

et al. 2024

Preprint

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Hepatocellular carcinoma (HCC) is a prevalent and aggressive malignancy with limited treatment options. Therefore, the identification of novel drug candidate target genes is crucial for the development of effective therapeutic strategies for HCC. In this study, we employed deeply bioinformatics analysis to identify potential therapeutic targets for HCC. Key genes were identified in HCC, and gene ontology (GO) and KEGG pathway networks were constructed to explore their biological functions and associated pathways. CDK1 and DLGAP5 were highly expressed in HCC and associated with poor prognosis. Additionally, CDK1 and DLGAP5 were found to be associated with tumor immune cell infiltration to promote HCC. These findings provide valuable insights into the development of novel therapeutic approaches for HCC.

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DLGAP5 knockdown inactivates the Wnt/β‐catenin signal to repress endometrial cancer cell malignant activities

Cited by 3 publications

References 55 publications

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

KIF15 knockdown inhibits the development of endometrial cancer by suppressing epithelial‐mesenchymal transition and stemness through Wnt/β‐catenin signaling

DLGAP5 promotes lung adenocarcinoma growth via upregulating PLK1 and serves as a therapeutic target

Bioinformatics Analysis Identified a Crucial Role of Tumor Immune Cell Infiltration in Hepatocellular Carcinoma

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