Roles of PI3K/AKT/mTOR Axis in Arteriovenous Fistula

Ratti, Stefano; Mauro, Raffaella; Rocchi, Cristina; Mongiorgi, Sara; Ramazzotti, Giulia; Gargiulo, Mauro; Cocco, Lucio; Fiume, Roberta

doi:10.3390/biom12030350

Cited by 5 publications

(5 citation statements)

References 58 publications

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“…High expression of EFNA4 is associated with tumor invasiveness and metastasis, making it an attractive therapeutic target. In previous studies, EFNA4 has been shown to function as an oncogene in a variety of malignancies and participate in the regulation of tumor cell growth and metastasis ( 8 - 12 ). In this study, through TCGA database analysis, we verified that EFNA4 is highly expressed in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Ephrin A4 ( EFNA4 ) is a ligand of the ephrin (EFN) family and is involved in the development of blood vessels and epithelium through the regulation of cell migration and repulsion ( 11 ). EFNA4 participates in the regulation of many signaling pathways, including the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway and EFN/EFN receptor (Eph) signaling pathway, among others ( 12 ). Previous study has shown that EFNA4 directly interacts with EFN receptor A2 (EPHA2) and promotes its phosphorylation at Ser897, recruits phosphoinositol-3-kinase regulatory subunit 2 (PIK3R2), and activates the glycogen synthase kinase-3β (GSK3β)/β-catenin signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

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The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis

Ye,

Chen,

Liu

et al. 2024

J Gastrointest Oncol

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Background Pancreatic cancer is a highly aggressive malignancy with poor prognosis, and there is an urgent need to understand its molecular mechanisms for early diagnosis and treatment. Despite surgical resection being the only effective treatment, most patients are diagnosed at an advanced stage, missing the optimal window for therapy. Identifying novel biomarkers is crucial for prognostic assessment, treatment planning, and early intervention. Ephrin A4 ( EFNA4 ), a member of the receptor tyrosine kinase family, is involved in vascular and epithelial development via regulation of cell migration and rejection. However, the role of EFNA4 in pancreatic cancer has not been reported. Therefore, our study aimed to clarify the role of EFNA4 in pancreatic cancer through bioinformatics analysis and vitro experiments. Methods The expression of EFNA4 and its potential value as a diagnostic and prognostic biomarker in pancreatic cancer was analyzed using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) database. According to the expression level of EFNA4 , patients were divided into high expression group and low expression group, and the correlation between overall survival (OS) and disease-free survival (DFS) with different expression levels of EFNA4 and clinical parameters were analyzed. Subsequently, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect EFNA4 expression. The proliferation, invasion, and cloning ability of the cells were detected via Cell Counting Kit 8 (CCK8), Transwell, and plate cloning assays, respectively. Results EFNA4 is highly expressed in pancreatic cancer, and upregulation of EFNA4 is associated with poor prognosis. In this study, EFNA4 expression was correlated with T stage and TNM (tumor-node-metastasis) stage of pancreatic cancer, and the median survival time and progression-free survival (PFS) were worse in those with high EFNA4 expression (394 days) than in those with low expression (525 days) [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.00–2.16, P=0.047]. In addition, EFNA4 was also found to be involved in the regulation of signal pathways such as cell adhesion, cyclic AMP, insulin secretion, pancreatic secretion, and protein digestion and absorption. In vitro experiments demonstrated that EFNA4 knockdown significantly inhibited the proliferation, cloning ability, and invasiveness of the PANC-1 and SW1990 pancreatic cancer cell lines. Conclusions The abnormal expression of EFNA4 in pancreatic cancer is associated with p...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis

Ye,

Chen,

Liu

et al. 2024

J Gastrointest Oncol

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“…Extracellular matrix components are expressed in various patterns during AVF maturation [ 48 , 49 ]. The PI3K-AKT signaling pathway is involved in multiple functions, including extracellular matrix formation, wall thickening remodeling, immune system activation, and inflammation reduction [ 50 ]. Furthermore, it often performs contrasting functions in the AVF process.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Arteriovenous Fistula Failure: Insights from Bioinformatics Analysis

Guo

et al. 2022

JCDD

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(1) Background: Arteriovenous fistulas (AVFs) are the preferred access for hemodialysis. Unfortunately, about 60% of patients, especially female patients, fail to receive normal dialysis within one year after surgery because of AVF failure. However, the underlying mechanisms caused by sex differences in AVF failure remain unclear. (2) Methods: We performed analysis of DEGs and functional analysis with the dataset GSE119296 to reveal the biology underlying AVF failure. Immune responses were calculated using CIBERSORT. A protein–protein interaction network and hub gene were constructed using STRING and stepwise identification of potential drugs was performed online. (3) Results: Functional analysis showed that extracellular matrix reprogramming and PI3K-AKT pathway enrichment were significant in both male and female patients. COL1A1 was the hub gene in male patients, whereas CDK1 was the hub gene in female patients. Immune responses including γδ-T cells and mast cells are activated in female patients while no significant differences were noted in the male group. (4) Conclusions: In this study, we used a series of mature and recognized bioinformatic strategies to determine the following items: (1) Reveal the pathogenesis of AVF failure through HUB genes and signaling pathways between the different sexes. (2) Determine the relationship between sex differences in AVF failure and immune abnormalities. (3) Search for relevant sex-specific drugs targeting AVF failure.

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“…The last one, class III PI3K, has only a catalytic subunit, VPS34 [96]. Regarding distribution, PI3Kα, PI3Kβ, PI3KC2α, and PI3KC2β isoforms are relatively ubiquitously expressed, PI3Kγ and PI3Kδ are found especially in leukocytes, while PI3KC2γ is found in the liver [98].…”

Section: Overview Of the Pi3k/akt/mtor Signaling Pathwaymentioning

confidence: 99%

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

Morgos,

Stefani,

Miricescu

et al. 2024

IJMS

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Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA, TP53, ARID1A, CDH1, Ras, Raf, and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)—PI3K/AKT/mTOR—and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity. Helicobacter pylori, growth factors, cytokines, hormones, and oxidative stress also activate both pathways, enhancing GC development. In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.

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Roles of PI3K/AKT/mTOR Axis in Arteriovenous Fistula

Cited by 5 publications

References 58 publications

The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis

The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis

Sex Differences in Arteriovenous Fistula Failure: Insights from Bioinformatics Analysis

Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

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