Analysis of Multiple Human Tumor Cases Reveals the Carcinogenic Effects of PKP3

Ruan, Shujie; Shi, Jingping; Wang, Ming; Zhu, Zhechen

doi:10.1155/2021/9391104

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Activation of the EGFR pathway leads to increased cell growth and tumor formation in many cancers, including melanoma. Other proteins related to melanoma progression and aggressiveness, such as WNT7B (Chen et al, 2023) , WNT5A (Bueno et al, 2022), WNT11 (Menck et al, 2021) (Wnt pathway) and other individual proteins (e.g., SFN (Shiba-Ishii, 2021), COL1A1 (Verginadis et al, 2022), CLDN4 (Hao et al, 2022), PKP3 (Ruan et al, 2021), and SDC1 (Maeda et al, 2006)), were highly connected in the PPI analysis. Overall, these results indicate that SRY target genes in samples with high SRY expression are implicated in cellular pathways associated with melanoma progression and aggressive tumors, supporting high SRY expression as a contributor to poor prognosis among men with melanoma (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

Unveiling the role of SRY in male-biased cancers: Insights into the molecular basis of sex disparities in high-grade glioma and melanoma

Guardia

Batista

Penalva³

et al. 2023

Preprint

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Sex disparities have been observed in many tumor types affecting non-reproductive organs. Typically, the incidence and mortality rates of such cancers are higher in men. Although differences in lifestyle and environmental exposures are known contributors, knowledge of the molecular mechanisms driving sexual dimorphism in tumor development and therapy response remains limited. To address this question, we comprehensively studied the sex-determining region Y (SRY) gene, a male-specific gene that is critical in development. First, we screened 2,448 samples from 11 cancer types to identify those with a higher incidence in men and increased expression of SRY. In cases of high-grade glioma and melanoma, men with tumors exhibiting high SRY expression had a worse prognosis. Our results suggest that SRY target genes show altered expression when SRY is overexpressed. These gene sets are linked to cell growth, epithelial-mesenchymal transition, inflammation, and repression of tumor suppressor pathways (TP53 activation and activity of immune cells). In summary, we present the first comprehensive investigation of SRY expression and its association with clinical outcomes in men with high-grade glioma and melanoma. Our results shed light on the molecular basis for sex disparities and lay the foundation for investigation of various target genes and novel cancer treatments in men with high-grade glioma and melanoma.

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Section: Resultsmentioning

confidence: 99%

Unveiling the role of SRY in male-biased cancers: Insights into the molecular basis of sex disparities in high-grade glioma and melanoma

Guardia

Batista

Penalva³

et al. 2023

Preprint

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“…PKP3 is a widely expressed member of the PKP family that is present in both monolayer and stratified epithelial tissues that contain desmosomes [ 24 ]. PKP3 plays a crucial role in the development and progression of cancer by promoting malignant biological activity and is considered an essential biomarker for early cancer diagnosis and prognosis evaluation [ 25 ]. The FOSL1 protein is commonly regarded as an integral subunit of the AP1 transcriptional complex.…”

Section: Discussionmentioning

confidence: 99%

Molecular map of disulfidptosis-related genes in lung adenocarcinoma: the perspective toward immune microenvironment and prognosis

Zhao,

Su,

Wang

et al. 2024

Clin Epigenet

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Background Disulfidptosis is a recently discovered form of programmed cell death that could impact cancer development. Nevertheless, the prognostic significance of disulfidptosis-related genes (DRGs) in lung adenocarcinoma (LUAD) requires further clarification. Methods This study systematically explores the genetic and transcriptional variability, prognostic relevance, and expression profiles of DRGs. Clusters related to disulfidptosis were identified through consensus clustering. We used single-sample gene set enrichment analysis and ESTIMATE to assess the tumor microenvironment (TME) in different subgroups. We conducted a functional analysis of differentially expressed genes between subgroups, which involved gene ontology, the Kyoto encyclopedia of genes and genomes, and gene set variation analysis, in order to elucidate their functional status. Prognostic risk models were developed using univariate Cox regression and the least absolute shrinkage and selection operator regression. Additionally, single-cell clustering and cell communication analysis were conducted to enhance the understanding of the importance of signature genes. Lastly, qRT-PCR was employed to validate the prognostic model. Results Two clearly defined DRG clusters were identified through a consensus-based, unsupervised clustering analysis. Observations were made concerning the correlation between changes in multilayer DRG and various clinical characteristics, prognosis, and the infiltration of TME cells. A well-executed risk assessment model, known as the DRG score, was developed to predict the prognosis of LUAD patients. A high DRG score indicates increased TME cell infiltration, a higher mutation burden, elevated TME scores, and a poorer prognosis. Additionally, the DRG score showed a significant correlation with the tumor mutation burden score and the tumor immune dysfunction and exclusion score. Subsequently, a nomogram was established for facilitating the clinical application of the DRG score, showing good predictive ability and calibration. Additionally, crucial DRGs were further validated by single-cell sequencing data. Finally, crucial DRGs were further validated by qRT-PCR and immunohistochemistry. Conclusion Our new DRG signature risk score can predict the immune landscape and prognosis of LUAD. It also serves as a reference for LUAD's immunotherapy and chemotherapy.

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“…Analogously, upregulation of PKP3 expression promotes the proliferation of prostate cancer and NSCLC 13,16 . Plakophilin 3 is also reported to mediate the infiltration of immune cells in the tumor matrix, which is deemed as the pivotal factor in regulating progression and metastasis of cancers 31 . Competitive binding of miR‐328‐3p and miR‐3173‐5p to circIGF2BP3 results in the upregulation of PKP3 expression, which promotes deubiquitinating enzyme otubain‐1 (OTUB1) expression by increasing its mRNA stability, and then prevents the proteasomal degradation of programmed cell death 1 ligand 1 (PD‐L1) by inducing its deubiquitination, and ultimately inhibits the activation and infiltration of CD8 + T cells in the tumor region and thus facilitates tumor immune evasion in NSCLC 32 …”

Section: Plakophilin 3 Plays Important Role In Cancer Progressionmentioning

confidence: 99%

Role and function of plakophilin 3 in cancer progression and skin disease

Zhang,

Chen,

Tian

et al. 2023

Cancer Science

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Plakophilin 3 (PKP3), a component of desmosome, is aberrantly expressed in many kinds of human diseases, especially in cancers. Through direct interaction, PKP3 binds with a series of desmosomal proteins, such as desmoglein, desmocollin, plakoglobin, and desmoplakin, to initiate desmosome aggregation, then promotes its stability. As PKP3 is mostly expressed in the skin, loss of PKP3 promotes the development of several skin diseases, such as paraneoplastic pemphigus, pemphigus vulgaris, and hypertrophic scar. Moreover, accumulated clinical data indicate that PKP3 dysregulates in diverse cancers, including breast, ovarian, colon, and lung cancers. Numerous lines of evidence have shown that PKP3 plays important roles in multiple cellular processes during cancer progression, including metastasis, invasion, tumor formation, autophagy, and proliferation. This review examines the diverse functions of PKP3 in regulating tumor formation and development in various types of cancers and summarizes its detailed mechanisms in the occurrence of skin diseases.

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Analysis of Multiple Human Tumor Cases Reveals the Carcinogenic Effects of PKP3

Cited by 8 publications

References 35 publications

Unveiling the role of SRY in male-biased cancers: Insights into the molecular basis of sex disparities in high-grade glioma and melanoma

Unveiling the role of SRY in male-biased cancers: Insights into the molecular basis of sex disparities in high-grade glioma and melanoma

Molecular map of disulfidptosis-related genes in lung adenocarcinoma: the perspective toward immune microenvironment and prognosis

Role and function of plakophilin 3 in cancer progression and skin disease

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