Prolyl-4-Hydroxylase α Subunit 2 as a Novel Potential Biomarker for Predicting the Prognosis of Epithelial Ovarian Carcinoma

Zhang, Haibo; Zhao, Wei

doi:10.2147/cmar.s302423

Cited by 3 publications

(4 citation statements)

References 28 publications

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“…Collagen is an essential component of the extracellular matrix [43], which can promote tumor development by initiating tumor cell proliferation, invasion, migration, epithelial-mesenchymal transition, and chemoresistance [44][45][46]. Abnormal P4HA2 expression indicates a poor outcome in liver, cervical, and ovarian cancers [47][48][49]. Aspirin represses P4HA2 expression through NF-κB and LMCD1-AS1/let-7 g pathways, inhibiting collagen deposition and preventing HCC progression [50].…”

Section: Discussionmentioning

confidence: 99%

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression

Tang,

Liu,

Tian

et al. 2023

BMC Complement Med Ther

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Background Corosolic acid is a pentacyclic triterpene acid with hypoglycemic, anti-inflammatory, and anti-cancer effects. However, its potential targets in hepatocellular carcinoma (HCC) are unknown, hindering clinical utilization. Methods Differentially expressed proteins of the Bel-7404 cell line were identified with tandem mass tag analysis and differentially expressed genes (DEGs) of an HCC TCGA dataset using bioinformatics. Gene functions and pathways were inferred using the DAVID database. Online databases were used to establish P4HA2 expression in HCC (GEPIA2) and its relationship with patient survival (UALCAN and The Human Protein Atlas), the association between P4HA2 expression and immune cell infiltration (TIMER2), and DNA methylation of the P4HA2 gene (MethSurv). Cell proliferation, cell cycle, and cell death were assessed with PI and SYTOX-Green staining, CCK-8, and colony formation assays. Protein expression levels were detected by Western blotting. Results A total of 44 differentially expressed proteins and 4498 DEGs were identified. Four genes whose proteins were also found in the differential protein profile but with opposing expressions were selected as candidate targets. The candidate gene prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was recognized as the only potential target due to its high expression in public datasets, association with poor patient survival, and relation to immune cell infiltration in HCC tissues. Moreover, the DNA methylation status in 4 CpG islands of the P4HA2 gene correlated with a poor prognosis. Furthermore, corosolic acid treatment inhibited the proliferation of HCC cell lines Bel-7404 and HepG2 in a dose-dependent manner, caused G2/M phase cell cycle arrest, and promoted cell death. In addition, the treatment reduced P4HA2 protein levels. Conclusion Our results indicate that P4HA2 is a potential target of corosolic acid. Thus, they contribute to understanding molecular changes in HCC after corosolic acid treatment and facilitate finding new treatment regimens.

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Section: Discussionmentioning

confidence: 99%

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression

Tang,

Liu,

Tian

et al. 2023

BMC Complement Med Ther

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“…Meanwhile, collagen is an important component of the extracellular matrix (ECM)(Gorres and Raines 2010), which can ultimately promote tumor development by promoting tumor cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and chemoresistance (Yang et al 2014;Zheng et al 2017;Yamazaki et al 2018). Recently, abnormal expression of P4HA2 has been continuously reported as a marker of poor disease prognosis in tumors such as liver cancer, cervical cancer, and ovarian cancer (Cao et al 2020;Zhang and Zhao 2021;Shang et al 2022). Simultaneously, it has also been shown that aspirin reduces the expression level of P4HA2 through the NF-κB and LMCD1-AS1/let-7g pathways, thereby inhibiting collagen deposition and preventing the progression of hepatocellular carcinoma (Wang et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Network pharmacological analysis of corosolic acid inhibits hepatocellular carcinoma progression through P4HA2

Tang

Liu

Tian

et al. 2022

Preprint

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Hepatocellular carcinoma (HCC) is a common cancer with very limited therapeutic options. Our previous study revealed that corosolic acid inhibited HCC proliferation and enhanced chemotherapy sensitivity. This study set out to identify the differentially expressed proteins of corosolic acid in the treatment of liver cancer cells, providing molecular targets for targeted therapy of liver cancer in the future. First, data on potential therapeutic targets regulated by corosolic acid were collected using proteomics. The enrichment analysis of GO and KEGG was used to identify the differentially expressed proteins. Differentially expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) liver cancer dataset were analyzed by using the DESeq2 R package. Then,databases such as GEPIA2, Human Protein Atlas, and UALCAN were used to validate the differential expression of DEGs and the prognostic relevance to patients. Finally, experiments were carried out to verify the effect of corosolic acid on hepatocellular carcinoma cell phenotype and the modulation of the screened target proteins. This study will help to understand the molecular changes of HCC after corosolic acid treatment, which will help to find new targets and design effective chemotherapy regimens for future HCC treatment.

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“…The prolyl 4‐hydroxylase subunit alpha 2 ( P4HA2 ) gene encodes a component of prolyl 4‐hydroxylase, a key enzyme in collagen synthesis 9 . Several studies have reported that P4HA2 is highly expressed in many cancers and participates in cancer progression 10–14 . These studies are often associated with collagen expression in cancers.…”

Section: Introductionmentioning

confidence: 99%

“…9 Several studies have reported that P4HA2 is highly expressed in many cancers and participates in cancer progression. [10][11][12][13][14] These studies are often associated with collagen expression in cancers. Collagen is the main structural protein component of the extracellular matrix (ECM), 15 and the biochemical and biophysical properties of ECM are essential for the survival, growth, invasion, and drug resistance of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

CEBPB upregulates P4HA2 to promote the malignant biological behavior in IDH1 wildtype glioma

Wang

Zhao

et al. 2023

The FASEB Journal

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Temozolomide (TMZ), the primary drug for glioma treatment, has limited treatment efficacy. Additionally, considerable evidence shows that isocitrate dehydrogenase 1 mutation-type (IDH1 mut) gliomas have a better response to TMZ than isocitrate dehydrogenase 1 wildtype (IDH1 wt) gliomas. Here, we aimed to identify potential mechanisms underlying this phenotype. Herein, the Cancer Genome Atlas bioinformatic data and 30 clinical samples from patients were analyzed to reveal the expression level of cytosine-cytosine-adenosineadenosine-thymidine (CCAAT) Enhancer Binding Protein Beta (CEBPB) and prolyl 4-hydroxylase subunit alpha 2 (P4HA2) in gliomas. Next, cellular and animal experiments, including cell proliferation, colony formation, transwell, CCK-8, and xenograft assays, were performed to explore the tumor-promoting effects of P4HA2 and CEBPB. Then, chromatin immunoprecipitation (ChIP) assays were used to confirm the regulatory relationships between them. Finally, a co-immunoprecipitation (Co-IP) assay was performed to confirm the effect of IDH1-132H to CEBPB proteins. We found that CEBPB and P4HA2 expression was significantly upregulated in IDH1 wt gliomas and associated with poor prognosis. CEBPB knockdown inhibited the proliferation, migration, invasion, and temozolomide resistance of glioma cells and hindered the growth of glioma xenograft tumors. CEBPE, as a transcription factor, exerted its function by transcriptionally upregulating P4HA2 expression in glioma cells. Importantly, CEBPB is prone to ubiquitin-proteasomal degradation in IDH1 R132H glioma cells. We also demonstrated that both genes are related to collagen synthesis, as confirmed by in vivo experiments. Thus, CEBPE promotes proliferation and TMZ

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Prolyl-4-Hydroxylase α Subunit 2 as a Novel Potential Biomarker for Predicting the Prognosis of Epithelial Ovarian Carcinoma

Cited by 3 publications

References 28 publications

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression

Network pharmacological analysis of corosolic acid inhibits hepatocellular carcinoma progression through P4HA2

CEBPB upregulates P4HA2 to promote the malignant biological behavior in IDH1 wildtype glioma

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