Dataset Information

Genome-Scale Metabolic Model Analysis of Metabolic Differences between Lauren Diffuse and Intestinal Subtypes in Gastric Cancer.

ABSTRACT: Gastric cancer (GC) is one of the most lethal cancers worldwide; it has a high mortality rate, particularly in East Asia. Recently, genetic events (e.g., mutations and copy number alterations) and molecular signaling associated with histologically different GC subtypes (diffuse and intestinal) have been elucidated. However, metabolic differences among the histological GC subtypes have not been studied systematically. In this study, we utilized transcriptome-based genome-scale metabolic models (GEMs) to identify differential metabolic pathways between Lauren diffuse and intestinal subtypes. We found that diverse metabolic pathways, including cholesterol homeostasis, xenobiotic metabolism, fatty acid metabolism, the MTORC1 pathway, and glycolysis, were dysregulated between the diffuse and intestinal subtypes. Our study provides an overview of the metabolic differences between the two subtypes, possibly leading to an understanding of metabolism in GC heterogeneity.

SUBMITTER: Nam S

PROVIDER: S-EPMC9104812 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Genome-Scale Metabolic Model Analysis of Metabolic Differences between Lauren Diffuse and Intestinal Subtypes in Gastric Cancer.

Nam Seungyoon S Lee Yongmin Y

Cancers 20220509 9

Gastric cancer (GC) is one of the most lethal cancers worldwide; it has a high mortality rate, particularly in East Asia. Recently, genetic events (e.g., mutations and copy number alterations) and molecular signaling associated with histologically different GC subtypes (diffuse and intestinal) have been elucidated. However, metabolic differences among the histological GC subtypes have not been studied systematically. In this study, we utilized transcriptome-based genome-scale metabolic models (G ...[more]

PMID: 35565469

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Project description:BackgroundSeveral genetic and epigenetic alterations are related to the development and progression of Gastric Cancer (GC), one of those being the deregulated microRNA (miRNA) expression profile. miRNAs are small noncoding RNAs that negatively regulate the expression of thousands of genes, including oncogenes and tumor suppressor genes. Our group identified, in previous studies, some miRNAs that are differentially expressed in GC when compared to the gastric mucosa without cancer, including hsa-miR-29c and hsa-miR-135b. The aim of the study was to modulate the expression of the miRNAs hsa-miR-29c-5p and hsa-miR-135b-5p and evaluate the expression of their target genes in 2D and 3D cell cultures.Methodshsa-miR-29c-5p and hsa-miR-135b-5p expression profiles were modulated by transfecting mimics and antimiRs, respectively, in 2D and 3D cell cultures. The expression of the proteins coded by the genes CDC42, DNMT3A (target genes of hsa-miR-29c-5p) and APC (target gene of hsa-miR-135b-5p) were measured by Western Blot.ResultsResults showed that mimics and antimiRs transfection significantly altered the expression of both miRNAs, increasing the expression of hsa-miR-29c-5p and reducing the expression of hsa-miR-135b-5p, especially in the 3D culture of the cell lines. When analyzing the proteins expression, we observed that AGP01 and AGP03 cell lines transfected with mimics had a reduction in the levels of CDC42 and DNMT3A and all three cell lines transfected with antimiRs had an increase in the expression of the protein APC.ConclusionWe concluded that three-dimensional culture can be a more representative in vitro model that resembles better the in vivo reality. Our results also showed that hsa-miR-29c-5p is an important regulator of CDC42 and DNMT3A genes in the intestinal subtype gastric cancer and hsa-miR-135b-5p regulates the APC gene in both intestinal and diffuse subtypes of GC. Dysregulation in their expression, and consequently in their respectively signaling pathways, shows how these miRNAs can influence the carcinogenesis of different histological subtypes of gastric cancer.

Dataset Information

Genome-Scale Metabolic Model Analysis of Metabolic Differences between Lauren Diffuse and Intestinal Subtypes in Gastric Cancer.

Publications

Genome-Scale Metabolic Model Analysis of Metabolic Differences between Lauren Diffuse and Intestinal Subtypes in Gastric Cancer.

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