WDHD1 facilitates G1 checkpoint abrogation in HPV E7 expressing cells by modulating GCN5

Yang, Zhou; Pei, Fengyan; Ji, Mingyu; Zhang, Fang; Sun, Yuchen; Zhao, Qianqian; Xiao, Wang; Hong, Yatian; Tian, Juanjuan; Wang, Yunshan; Chen, Jason J.

doi:10.1186/s12885-020-07287-1

Cited by 8 publications

(8 citation statements)

References 53 publications

(79 reference statements)

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“…Recent studies have observed the overexpression of WDHD1 in the great majority of lung cancers and esophageal squamous cell carcinomas ( Sato et al, 2010 ). WDHD1 has also been reported to facilitate the abrogation of G1 checkpoint upon DNA damage, leading to genomic instability and eventually tumorigenesis ( Zhou et al, 2020 ). Moreover, WDHD1 could accelerate cell proliferation, cell viability, and metastasis in several cancers including cholangiocarcinoma and breast cancer ( Sato et al, 2010 ; Liu et al, 2019 ; Ertay et al, 2020 ; Zhou and Chen, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of Survival-Associated Hub Genes in Pancreatic Adenocarcinoma Based on WGCNA

Huang¹,

Ye²,

Wang³

et al. 2022

Front. Genet.

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Pancreatic adenocarcinoma is one of the leading causes of cancer-related death worldwide. Since little clinical symptoms were shown in the early period of pancreatic adenocarcinoma, most patients were found to carry metastases when diagnosis. The lack of effective diagnosis biomarkers and therapeutic targets makes pancreatic adenocarcinoma difficult to screen and cure. The fundamental problem is we know very little about the regulatory mechanisms during carcinogenesis. Here, we employed weighted gene co-expression network analysis (WGCNA) to build gene interaction network using expression profile of pancreatic adenocarcinoma from The Cancer Genome Atlas (TCGA). STRING was used for the construction and visualization of biological networks. A total of 22 modules were detected in the network, among which yellow and pink modules showed the most significant associations with pancreatic adenocarcinoma. Dozens of new genes including PKMYT1, WDHD1, ASF1B, and RAD18 were identified. Further survival analysis yielded their valuable effects on the diagnosis and treatment of pancreatic adenocarcinoma. Our study pioneered network-based algorithm in the application of tumor etiology and discovered several promising regulators for pancreatic adenocarcinoma detection and therapy.

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Section: Resultsmentioning

confidence: 99%

Identification of Survival-Associated Hub Genes in Pancreatic Adenocarcinoma Based on WGCNA

Huang¹,

Ye²,

Wang³

et al. 2022

Front. Genet.

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“…However, research on the mechanism of WDHD1 in cancer has not been extensive. Several studies have linked the WDHD1 gene to key processes such as tumorigenesis and metastasis [ 18 , 63 , 64 ]. For example, Li et al proposed that WDHD1 could regulate the stability of the GCN5 protein and the acetylation of histone H3 with remarkable precision, which might play an important role in tumor cell growth [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Integrative bioinformatics analysis of WDHD1: a potential biomarker for pan-cancer prognosis, diagnosis, and immunotherapy

Cui,

Zou,

Wang

et al. 2023

World J Surg Onc

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Background Although WD repeat and high-mobility group box DNA binding protein 1 (WDHD1) played an essential role in DNA replication, chromosome stability, and DNA damage repair, the panoramic picture of WDHD1 in human tumors remains unclear. Hence, this study aims to comprehensively characterize WDHD1 across 33 human cancers. Methods Based on publicly available databases such as TCGA, GTEx, and HPA, we used a bioinformatics approach to systematically explore the genomic features and biological functions of WDHD1 in pan-cancer. Results WDHD1 mRNA levels were significantly increased in more than 20 types of tumor tissues. Elevated WDHD1 expression was associated with significantly shorter overall survival (OS) in 10 tumors. Furthermore, in uterine corpus endometrial carcinoma (UCEC) and liver hepatocellular carcinoma (LIHC), WDHD1 expression was significantly associated with higher histological grades and pathological stages. In addition, WDHD1 had a high diagnostic value among 16 tumors (area under the ROC curve [AUC] > 0.9). Functional enrichment analyses suggested that WDHD1 probably participated in many oncogenic pathways such as E2F and MYC targets (false discovery rate [FDR] < 0.05), and it was involved in the processes of DNA replication and DNA damage repair (p.adjust < 0.05). WDHD1 expression also correlated with the half-maximal inhibitory concentrations (IC50) of rapamycin (4 out of 10 cancers) and paclitaxel (10 out of 10 cancers). Overall, WDHD1 was negatively associated with immune cell infiltration and might promote tumor immune escape. Our analysis of genomic alterations suggested that WDHD1 was altered in 1.5% of pan-cancer cohorts and the “mutation” was the predominant type of alteration. Finally, through correlation analysis, we found that WDHD1 might be closely associated with tumor heterogeneity, tumor stemness, mismatch repair (MMR), and RNA methylation modification, which were all processes associated with the tumor progression. Conclusions Our pan-cancer analysis of WDHD1 provides valuable insights into the genomic characterization and biological functions of WDHD1 in human cancers and offers some theoretical support for the future use of WDHD1-targeted therapies, immunotherapies, and chemotherapeutic combinations for the management of tumors.

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“…Our data support the notion that STAT3 regulates WDHD1 transcription and therefor promotes DNA replication. Interestingly, both STAT3 and WDHD1 have been implicated in cell cycle checkpoint control, epithelial-mesenchymal transition, tumor growth and metastasis [36,37,48,49] and reviewed in [50,51]. It would be interesting to examine whether STAT3 performs these functions through WDHD1.…”

Section: Discussionmentioning

confidence: 99%

STAT3 plays an important role in DNA replication by turning on WDHD1

Yang

Chen

2021

Cell Biosci

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Background Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that plays a key role in many cellular processes such as cell growth and cancer. However, the functions and mechanisms by which STAT3 regulates cellular processes are not fully understood. Results Here we describe a novel function of STAT3. We demonstrated that STAT3 plays an important role in DNA replication. Specifically, knockdown of STAT3 reduced DNA replication while activation and ectopic expression of STAT3 promoted DNA replication. We further identified the WD repeat and HMG-box DNA-binding protein 1 (WDHD1), which plays an important role in DNA replication initiation, as a novel STAT3 target gene that mediated the DNA replication function of STAT3. We showed that STAT3 bind the promoter/up regulatory region of WDHD1 gene. Conclusions These studies identified a novel function of STAT3 that is mediated by its newly identified target gene WDHD1 and have important implications.

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WDHD1 facilitates G1 checkpoint abrogation in HPV E7 expressing cells by modulating GCN5

Cited by 8 publications

References 53 publications

Identification of Survival-Associated Hub Genes in Pancreatic Adenocarcinoma Based on WGCNA

Identification of Survival-Associated Hub Genes in Pancreatic Adenocarcinoma Based on WGCNA

Integrative bioinformatics analysis of WDHD1: a potential biomarker for pan-cancer prognosis, diagnosis, and immunotherapy

STAT3 plays an important role in DNA replication by turning on WDHD1

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