MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

Wang, Yangyang; Zhou, Yao-Qi; Xie, Jia-Xuan; Zhang, Xiang; Wang, Shuchang; Li, Qing; Hu, Li-Peng; Jiang, Shu-Heng; Yi, Shuang-Qin; Xu, Jia; Cao, Hui; Zhao, Enyue; Li, Jun

doi:10.1007/s13402-023-00821-w

Cited by 13 publications

(6 citation statements)

References 41 publications

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“…Abnormalities of the PI3K/AKT/mTOR pathway are observed in the majority of malignancies including GC, and participate in diverse physiological processes such as cell proliferation, metastasis, and chemoresistance. 20,21 Notably, the PI3K/AKT/ mTOR pathway was able to promote the carcinogenesis of GC by increasing post-translational phosphorylation. 22 Additionally, our previous study showed that G6PC facilitated the advancement of cervical cancer by activating the PI3K/AKT/mTOR signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

The FOXO1/G6PC axis promotes gastric cancer progression and mediates 5‐fluorouracil resistance by targeting the PI3K/AKT/mTOR signaling pathway

Han,

Liu,

et al. 2024

Molecular Carcinogenesis

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Gastric cancer (GC) is a prevalent malignancy of the digestive system. Distant metastasis and chemotherapy resistance are the crucial obstacles to prognosis in GC. Recent research has discovered that the glucose‐6‐phosphatase catalytic subunit (G6PC) plays an important role in tumor malignant development. However, little evidence has highlighted its role in GC. Herein, through a comprehensive analysis including profiling of tissue samples and functional validation in vivo and in vitro, we identify G6PC as a crucial factor in GC tumorigenesis. Importantly, we found that the FOXO1/G6PC axis could accelerate GC cell proliferation, metastasis, and 5‐Fluorouracil (5‐FU) resistance by targeting the PI3K/AKT/mTOR signaling pathway, implicating that as a prospective therapeutic approach in GC.

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Section: Discussionmentioning

confidence: 99%

The FOXO1/G6PC axis promotes gastric cancer progression and mediates 5‐fluorouracil resistance by targeting the PI3K/AKT/mTOR signaling pathway

Han,

Liu,

et al. 2024

Molecular Carcinogenesis

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“…The PI3K/AKT signaling pathway can be abnormally activated in most cancers, promoting tumor cell proliferation, inhibiting apoptosis, and enhancing invasion and metastasis[ 25 ]. Wang et al [ 26 ] verified that monoamine oxidase A inhibits the progression of GC by reducing glycolysis through the PI3K/Akt/mTOR pathway. Inhibition of the PI3K/Akt pathway may provide a potential method for GC treatment.…”

Section: Discussionmentioning

confidence: 99%

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

Ma,

Zhang,

Sun

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Gastric cancer (GC) is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis. Resveratrol, a non-flavonoid polyphenolic compound found in a variety of Chinese medicinal materials, has shown excellent anti-GC effect. However, its exact mechanisms of action in GC have not been clarified. AIM To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms. METHODS Action targets of resveratrol and GC-related targets were screened from public databases. The overlapping targets between the two were confirmed using a Venn diagram, and a “Resveratrol-Target-GC” network was constructed using Cytoscape software version 3.9.1. The protein-protein interaction (PPI) network was constructed using STRING database and core targets were identified by PPI network analysis. The Database for Annotation, Visualization and Integrated Discovery database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A “Target-Pathway” network was created by using Cytoscape 3.9.1. The RNA and protein expression levels of core target genes were observed using the Cancer Genome Atlas and the Human Protein Atlas databases. DriverDBv3 and Timer2.0 databases were used for survival and immune infiltration analysis. Subsequently, the findings were further verified by molecular docking technology and in vitro experiments. RESULTS A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases, and 181 intersection targets between the two were screened by Venn diagram. The top 20 core targets were identified by PPI network analysis of the overlapping targets. GO function analysis mainly involved protein binding, identical protein binding, cytoplasm, nucleus, negative regulation of apoptotic process and response to xenobiotic stimulus. KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, ErbB signaling pathway, etc . FBJ murine osteosarcoma viral oncogene homolog (FOS) and matrix metallopeptidase 9 (MMP9) were selected by differential expression analysis, and they were closely associated with immune infiltration. Molecular docking results showed that resveratrol docked well with these two targets. Resveratrol treatment arrested the cell cycle at the S phase, induced apoptosis, and weakened viability, migration and invasion in a dose-dependent manner. Furthermore, resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression. CONCLUSION The anti-GC effects of resveratrol are related to the inhibition of cell proliferation, migration, invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

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“…However, this study did not delve into the molecular mechanisms of MAOA in gastric cancer development or consider its expression in gastric cancer tissues for clinical relevance. Another study mentioned that MAOA can interact with NDRG1, inhibiting downstream PI3K/AKT/mTOR pathway activity, thereby attenuating the Warburg effect in gastric cancer cells and ultimately suppressing tumor cell proliferation and malignant behavior [ 9 ]. These conflicting results warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…However, in cancer-related research, the release of 5-HT has been associated with tumor progression, and 5-HT acts as a growth factor for prostate cancer (PCa) cells [ 5 ]. Furthermore, elevated MAOA expression is linked to high-grade PCa and contributes to a poorly differentiated phenotype [ 6 – 9 ]. Studies have also indicated that MAOA expression is significantly downregulated in gastric cancer tissue.…”

Section: Introductionmentioning

confidence: 99%

A study predicting long-term survival capacity in postoperative advanced gastric cancer patients based on MAOA and subcutaneous muscle fat characteristics

Han,

Chang,

Wang

et al. 2024

World J Surg Onc

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Background The prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored. Methods We Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model’s performance. Results The enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram’s good predictive performance and clinical utility. Conclusion Integrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

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MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway

Cited by 13 publications

References 41 publications

The FOXO1/G6PC axis promotes gastric cancer progression and mediates 5‐fluorouracil resistance by targeting the PI3K/AKT/mTOR signaling pathway

The FOXO1/G6PC axis promotes gastric cancer progression and mediates 5‐fluorouracil resistance by targeting the PI3K/AKT/mTOR signaling pathway

Identification of anti-gastric cancer effects and molecular mechanisms of resveratrol: From network pharmacology and bioinformatics to experimental validation

A study predicting long-term survival capacity in postoperative advanced gastric cancer patients based on MAOA and subcutaneous muscle fat characteristics

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