CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma

Chang, Shih‐Lun; Chen, Tzu‐Ju; Lee, Ying-En; Lee, Sung‐Wei; Lin, Li‐Ching; He, Hao

doi:10.7150/ijms.25065

Cited by 18 publications

(21 citation statements)

References 25 publications

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“…The specific mechanism regarding the impact of CDKN3 overexpression on patient survival necessitates further exploration. Most studies have shown that CDKN3 overexpression is associated with the cell cycle, DNA replication, et al, thereby promoting tumor progression 4,6. Our study also showed that CDKN3 plays an important role in the proliferation of ESCA cells.…”

Section: Discussionsupporting

confidence: 80%

“…Overexpression of CDKN3 has been found in numerous human cancers,4,5,6 but the mechanism of CDKN3 overexpression has not been clear. Chau-Ting Yeh discovered that multiple forms of CDKN3 mutants and aberrant transcripts were present in hepatocellular cancerous tissues, but not in hepatitis tissues 15.…”

Section: Discussionmentioning

confidence: 99%

“…Binding of CDKN3 to CDK1/CDK2 results in dephosphorylation of the activated residues and an inhibition of CDK activities 3. Despite the negative regulatory effects of CDKN3 on CDK1 and CDK2, aberrant overexpression of CDKN3 has been implicated in numerous human cancers including prostate cancer,4 gastric cancer,5 and nasopharyngeal carcinoma,6 et al CDKN3 promotes tumor growth, migration, invasion and other aggressive biological processes,5 but its precise mechanism in the regulation of ESCA progression remains unknown. Therefore, this study aimed to explore the role of CDKN3 in ESCA.…”

Section: Introductionmentioning

confidence: 99%

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<p>CDKN3 promotes tumor progression and confers cisplatin resistance via RAD51 in esophageal cancer</p>

Wang¹,

Che²,

Wang³

et al. 2019

CMAR

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Purpose: Esophageal cancer (ESCA) progression and chemoresistance are critical factors that impact the survival of patients with esophageal cancer. Cyclin dependent kinase inhibitor 3 (CDKN3) is an important regulator of the cell cycle that has received little attention, therefore the purpose of this study was to investigate CDKN3 involvement in ESCA. Methods: We first explored the public database in addition to our cohort to evaluate the expression of CDKN3 in ESCA patients. We performed bioinformative analysis on specific processes regulated by CDKN3, then we investigated the role of CDKN3 in ESCA progression and chemoresistance in vitro and in vivo. Finally, we sought to elucidate the mechanism of CDKN3 regulation of chemoresistance in ESCA. Results: We discovered that CDKN3 was highly expressed in ESCA and serves as an independent prognostic factor of this disease. Bioinformatic analysis showed CDKN3 involvement in DNA replication, the cell cycle G2/M phase transition, DNA damage repair (DDR) signaling pathways, et al Functional experiments in vitro and in vivo demonstrated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance. Furthermore, CDKN3 inhibition resulted in reduced expression of RAD51, which plays a pivotal role in DDR. Overexpression of RAD51 reversed cisplatin-induced DNA damage and chemosensitivity in CDKN3 inhibited ESCA cell lines. Conclusion: The present research indicated that CDKN3 promoted ESCA progression and enhanced cisplatin resistance via RAD51, thereby influencing overall patient survival.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>CDKN3 promotes tumor progression and confers cisplatin resistance via RAD51 in esophageal cancer</p>

Wang¹,

Che²,

Wang³

et al. 2019

CMAR

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“…CDKN3 has been reported to be involved in tumor development and progression (14)(15)(16)(17). Chang et al (26) have demonstrated that CDKN3 is overexpressed in nasopharyngeal cancer (NPC) tissues and that high expression of CDKN3 is associated with an advanced tumor stage and poor survival; thus, CDKN3 may serve as a predictive target for NPC. In cervical cancer, the expression of CDKN3 is associated with poor survival, and silencing CDKN3 expression significantly reduces cell proliferation (15).…”

Section: Discussionmentioning

confidence: 99%

“…The AKT signaling pathway serves important roles in inducing the cell cycle, proliferation and invasion. Therefore, the protein levels of the vital genes involved in the AKT signaling pathway (26)(27)(28) were determined in the present study. The results demonstrated that knockdown of CDKN3 suppressed the phosphorylation of AKT and the expression of cyclin D1 and upregulated the expression of p27.…”

Section: Discussionmentioning

confidence: 99%

CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma

Yao

et al. 2019

Oncol Lett

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In China, esophageal squamous cell carcinoma (ESCC), capable of direct invasion and early metastasis, exhibits high mortality. Identification of the molecular basis driving ESCC progression and development of new diagnostic biomarkers are urgently needed. Cyclin-dependent kinase inhibitor 3 (CDKN3) performs crucial roles in the modulation of tumor development. The present study aimed to explore the functions and underlying mechanism of CDKN3 in regulating ESCC cell proliferation and invasion. The expression levels of CDKN3 in ESCC cells were evaluated by reverse transcription-quantitative PCR. Cell counting kit-8 and colony forming assays were used to evaluate cell viability. Wound-healing assay was performed to explore cell migration. Transwell invasion analysis was conducted to investigate the invasive capacity of ESCC cells. Protein levels were detected by western blot assay. The results demonstrated that the expression of CDKN3 was significantly upregulated in ESCC tissues, as predicted using the UALCAN and Gene Expression Omnibus databases. PCR and western blot assays confirmed that CDKN3 was upregulated in ESCC cell lines. Functional assays revealed that CDKN3 knockdown with small interfering RNA decreased the ability of ESCC cells to proliferate, invade and migrate and suppressed G1/S transition. Further mechanistic analyses demonstrated that CDKN3 promoted cell proliferation and invasion by activating the AKT signaling pathway in ESCC cells. To the best of our knowledge, the present study is the first to identify the functions of CDKN3 in ESCC and provide evidence that CDKN3 regulates tumor progression by activating the AKT signaling pathway. Therefore, CDKN3 may serve as a potential effective therapeutic target for ESCC treatment.

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Prognostic and immunological implications of paraptosis‐related genes in lung adenocarcinoma: Comprehensive analysis and functional verification of hub gene

Zhuo,

Song

2024

Environmental Toxicology

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BackgroundLung adenocarcinoma (LUAD) poses significant clinical challenges due to its inherent heterogeneity and variable response to treatment. Recent research has specifically focused on elucidating the role of Paraptosis‐related genes (PRGs) in the progression of cancer and the prognosis of patients.MethodsWe conducted a comprehensive analysis of the differential expression of PRGs in LUAD. Additionally, univariate Cox regression analysis was utilized to determine the prognostic significance of these genes. Furthermore, consensus clustering was employed to differentiate molecular subtypes within LUAD, while immune heterogeneity was assessed. To evaluate treatment outcomes, the expression of immune checkpoint inhibitors was examined, and the sensitivity of LUAD patients to chemotherapy drugs was assessed. Moreover, machine learning algorithms were employed to construct a Paraptosis‐related risk score with prognostic and immunological indicators. Finally, to validate the findings, in vitro experiments were performed to verify the regulatory effect of key PRGs on Paraptosis.ResultsOur analysis identified 24 PRGs that exhibited differential expression, with CDKN3, TP53, and PHB emerging as the most prominently upregulated genes in tumor tissues. Among these genes, seven were identified as prognostic markers, with HSPB8 being the sole protective factor. Notably, our analysis also revealed the existence of two distinct molecular subtypes within LUAD, each characterized by unique prognoses and immune responses. Specifically, Subtype B displayed a poorer prognosis but demonstrated increased sensitivity to both chemotherapy and immunotherapy. In addition, our development of a Paraptosis‐Associated Risk Score yielded a significant prognostic value in predicting patient outcomes. Furthermore, we found regulatory effect of CDKN3 on Paraptosis in two cell lines.ConclusionsOur study highlights the importance of PRGs in LUAD, particularly in prognosis and treatment response. The identified molecular subtypes and Paraptosis‐Associated Risk Score offer valuable insights for personalized treatment strategies.

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CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma

Cited by 18 publications

References 25 publications

<p>CDKN3 promotes tumor progression and confers cisplatin resistance via RAD51 in esophageal cancer</p>

<p>CDKN3 promotes tumor progression and confers cisplatin resistance via RAD51 in esophageal cancer</p>

CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma

Prognostic and immunological implications of paraptosis‐related genes in lung adenocarcinoma: Comprehensive analysis and functional verification of hub gene

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