APC gene is modulated by hsa-miR-135b-5p in both diffuse and intestinal gastric cancer subtypes

Several 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...

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Published in:	BMC cancer 2018-10, Vol.18 (1), p.1055-10, Article 1055
Main Authors:	Magalhães, Leandro, Quintana, Luciana Gonçalves, Lopes, Dielly Catrina Favacho, Vidal, Amanda Ferreira, Pereira, Adenilson Leão, D'Araujo Pinto, Lara Carolina, de Jesus Viana Pinheiro, João, Khayat, André Salim, Goulart, Luiz Ricardo, Burbano, Rommel, de Assumpção, Paulo Pimentel, Ribeiro-Dos-Santos, Ândrea
Format:	Article
Language:	eng
Subjects:	3D culture Adenomatous polyposis coli Adenomatous polyposis coli protein Carcinogenesis CDC42 Cdc42 protein Cell culture Cell Line, Tumor Chromosome 5 Computational Biology - methods DNMT3A Epigenetics Gastric cancer Gastric mucosa Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes, APC Genetic aspects Hsa-miR-135b-5p Hsa-miR-29c-5p Humans Intestine MicroRNA MicroRNAs MicroRNAs - genetics miRNA Models, Biological Neoplasm Grading Neoplasm Staging RNA Interference Stem cells Stomach cancer Stomach Neoplasms - genetics Stomach Neoplasms - pathology Transcriptome Transfection Tumor suppressor genes Tumorigenesis
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Summary:	Several 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. hsa-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. Results 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. We 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.
ISSN:	1471-2407 1471-2407