CDCA8 Contributes to the Development and Progression of Thyroid Cancer through Regulating CDK1

Xiang, Cheng; Sun, Wu-Hui; You, Ke; Lei, Yu; Wang, Yong

doi:10.7150/jca.64747

Cited by 12 publications

(4 citation statements)

References 45 publications

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“…Previous studies have documented the functional relevance of CDCA8 in tumor cell apoptosis [ 21 , 22 ]. And first, to confirm the knockdown and overexpression efficiency, the qRT-PCR and Western blot analyses (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

CDCA8 promotes bladder cancer survival by stabilizing HIF1α expression under hypoxia

Zhou,

Huang,

Xiong

et al. 2023

Cell Death Dis

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Hypoxia is an essential hallmark of solid tumors and HIF1α is a central regulator of tumor cell adaptation and survival in the hypoxic environment. In this study, we explored the biological functions of cell cycle division-related gene 8 (CDCA8) in bladder cancer (BCa) cells in the hypoxic settings. Specifically, we found that CDCA8 was significantly upregulated in BCa cell lines and clinical samples and its expression was positively correlated with advanced BCa stage, grade, and poor overall survival (OS). The expression of CDCA8 proteins was required for BCa cells to survive in the hypoxic condition. Mechanistically, CDCA8 stabilizes HIF1α by competing with PTEN for AKT binding, consequently leading to PTEN displacement and activation of the AKT/GSK3β signaling cascade that stimulates HIF1α protein stability. Significantly, HIF1α proteins bind to CDCA8 promoter for transcriptional activation, forming a positive-feedback loop to sustain BCa tumor cells under oxygen-deficient environment. Together, we defined CDCA8 as a key regulator for BCa cells to sense and prevail oxygen deprivation and as a novel BCa therapeutic target.

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Section: Resultsmentioning

confidence: 99%

CDCA8 promotes bladder cancer survival by stabilizing HIF1α expression under hypoxia

Zhou,

Huang,

Xiong

et al. 2023

Cell Death Dis

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“…In previous studies [21,22], CDCA8 has been shown to be strongly associated with apoptosis in cancer cells. However, in our study, it was surprising that under normal cell culture conditions, the effect of CDCA8 expression status on Bca cells viability was negligible (Fig.…”

Section: Cdca8 Promotes Bca Cell Survival In Oxygen-deprived Environmentmentioning

confidence: 87%

CDCA8 promotes bladder cancer survival by stabilizing HIF1α expression under hypoxic

Guo

Zhou

Huang³

et al. 2023

Preprint

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Hypoxia is an essential feature of solid tumors. The regulatory network behind tumor cells in response to hypoxia environment is not completely comprehend. We ascertained the biochemical role of cell cycle division-related gene 8 (CDCA8) in bladder cancer (Bca) survival under hypoxia environment. In current study we revealed the expression of CDCA8 was considerably upraised in BCa. High expression level of CDCA8 was positive related with advanced Bca stage, advanced Bca stage grade and poor survival. Increased CDCA8 expression was decisive for Bca cells to survive in a hypoxic condition. CDCA8 enhanced the stabilization of HIF1α by competitively binding to AKT with PTEN and alleviating PTEN suppression to activate AKT phosphorylation, while HIF1α transcriptionally promote CDCA8 transcription, thus forming a positive feedback loop in Bca adaptation to oxygen-deficient environment. Collectively, CDCA8 promotes Bca survival under hypoxic environment by activating AKT/GSK3β signaling pathway and heightening the stabilization of HIF1α. CDCA8 is critical for Bca to adapt to oxygen deprivation and may provide a novel thinking for Bca treatment.

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“…CDCA8 stands as a pivotal regulatory gene in mitosis [27], exerting a crucial influence in various cancers by promoting cell proliferation and invasion, potentially functioning as an oncogene [28,29]. Earlier research has documented heightened transcriptional activity of CDCA8 in embryos, embryonic stem cells, and cancer cells [30,31]. However, a thorough pan-cancer investigation into the status of CDCA8 has not been undertaken until now.…”

Section: Discussionmentioning

confidence: 99%

CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology

2024

Am J Transl Res

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Background: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers. Methods: Bioinformatics and molecular experiments. Results: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines . Conclusion: This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.

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CDCA8 Contributes to the Development and Progression of Thyroid Cancer through Regulating CDK1

Cited by 12 publications

References 45 publications

CDCA8 promotes bladder cancer survival by stabilizing HIF1α expression under hypoxia

CDCA8 promotes bladder cancer survival by stabilizing HIF1α expression under hypoxia

CDCA8 promotes bladder cancer survival by stabilizing HIF1α expression under hypoxic

CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology

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