PPP1R14B is a diagnostic prognostic marker in patients with uterine corpus endometrial carcinoma

He, Kang; Wang, Taiwei; Huang, Xuemiao; Yang, Zhaoyun; Wang, Zeyu; Zhang, Shuang; Sui, Xin; Jiang, Junjie; Zhao, Lijing

doi:10.1111/jcmm.17697

Cited by 6 publications

(2 citation statements)

References 65 publications

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“…However, recent research conducted over the past decade has continuously reinforced PHI-1's significance in cell proliferation, consistently linking it to unfavorable clinical outcomes. Most notably, PHI-1 upregulation has been consistently observed across various malignancies, including ovarian clear cell carcinoma, chronic lymphocytic leukemia, prostate cancer, glioblastoma, triple-negative breast cancer, and uterine corpus endometrial carcinoma [32][33][34]37,38,55]. Furthermore, strong correlations between heightened PHI-1 expression levels and poorer prognoses have been established across various cancer types [33,35,37,38].…”

Section: Discussionmentioning

confidence: 99%

PHI-1, an Endogenous Inhibitor Protein for Protein Phosphatase-1 and a Pan-Cancer Marker, Regulates Raf-1 Proteostasis

Kirkbride,

Nilsson,

Kim

et al. 2023

Biomolecules

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Raf-1, a multifunctional kinase, regulates various cellular processes, including cell proliferation, apoptosis, and migration, by phosphorylating MAPK/ERK kinase and interacting with specific kinases. Cellular Raf-1 activity is intricately regulated through pathways involving the binding of regulatory proteins, direct phosphorylation, and the ubiquitin–proteasome axis. In this study, we demonstrate that PHI-1, an endogenous inhibitor of protein phosphatase-1 (PP1), plays a pivotal role in modulating Raf-1 proteostasis within cells. Knocking down endogenous PHI-1 in HEK293 cells using siRNA resulted in increased cell proliferation and reduced apoptosis. This heightened cell proliferation was accompanied by a 15-fold increase in ERK1/2 phosphorylation. Importantly, the observed ERK1/2 hyperphosphorylation was attributable to an upregulation of Raf-1 expression, rather than an increase in Ras levels, Raf-1 Ser338 phosphorylation, or B-Raf levels. The elevated Raf-1 expression, stemming from PHI-1 knockdown, enhanced EGF-induced ERK1/2 phosphorylation through MEK. Moreover, PHI-1 knockdown significantly contributed to Raf-1 protein stability without affecting Raf-1 mRNA levels. Conversely, ectopic PHI-1 expression suppressed Raf-1 protein levels in a manner that correlated with PHI-1’s inhibitory potency. Inhibiting PP1 to mimic PHI-1’s function using tautomycin led to a reduction in Raf-1 expression. In summary, our findings highlight that the PHI-1-PP1 signaling axis selectively governs Raf-1 proteostasis and cell survival signals.

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Section: Discussionmentioning

confidence: 99%

PHI-1, an Endogenous Inhibitor Protein for Protein Phosphatase-1 and a Pan-Cancer Marker, Regulates Raf-1 Proteostasis

Kirkbride,

Nilsson,

Kim

et al. 2023

Biomolecules

View full text Add to dashboard Cite

show abstract

“…In this experiment, we meticulously replicated the immunohistochemistry (IHC) staining technique described in a prior study (22). The process began with the sample undergoing a 24-hour xation in 10% formalin at room temperature, followed by embedding in para n wax, resulting in sections of 3µm thickness.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Exploring the Potential of CPA4 Knockdown as a Prognostic Biomarker in Inhibiting Endometrial Cancer Proliferation

He,

Zheng,

Zhang

et al. 2024

Preprint

Self Cite

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Background: The rise in endometrial cancer rates globally calls for advanced diagnostic methods and new biomarkers. CPA4, known for its role in cancer development, has not yet been studied in relation to endometrial cancer, making it a promising research avenue. Methods: We analyzed CPA4's mRNA expression using data from TCGA and GEO databases and validated these findings with 116 clinical samples through immunohistochemical analysis. The Ishikawa and Hec-1-A cell lines were used to examine CPA4's functionality. Additionally, we conducted correlation analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and survival analysis to understand CPA4's role in endometrial cancer prognosis. A nomogram model was developed for clinical prognostic predictions. Results: CPA4 is significantly overexpressed in endometrial cancer, correlating with tumor progression and poor prognosis. Overexpression is linked to crucial functions like mitosis and cell cycle. Reducing CPA4 in cell lines inhibited tumor growth and spread. Kaplan-Meier plots and Cox regression analysis confirmed CPA4's significance in prognosis, with our predictive model showing high accuracy. Conclusion: CPA4 emerges as a vital biomarker for diagnosing and prognosing endometrial cancer, presenting a novel pathway for research and clinical application. The study highlights its potential as a clinical tool, paving the way for improved patient management and treatment strategies in endometrial cancer.

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Lysine lactylation-based insight to understanding the characterization of cervical cancer

He,

Zhang,

Bai

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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PPP1R14B is a diagnostic prognostic marker in patients with uterine corpus endometrial carcinoma

Cited by 6 publications

References 65 publications

PHI-1, an Endogenous Inhibitor Protein for Protein Phosphatase-1 and a Pan-Cancer Marker, Regulates Raf-1 Proteostasis

PHI-1, an Endogenous Inhibitor Protein for Protein Phosphatase-1 and a Pan-Cancer Marker, Regulates Raf-1 Proteostasis

Exploring the Potential of CPA4 Knockdown as a Prognostic Biomarker in Inhibiting Endometrial Cancer Proliferation

Lysine lactylation-based insight to understanding the characterization of cervical cancer

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