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miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model

Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as tu...

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Autores principales: Streleckiene, Greta, Inciuraite, Ruta, Juzenas, Simonas, Salteniene, Violeta, Steponaitiene, Ruta, Gyvyte, Ugne, Kiudelis, Gediminas, Leja, Marcis, Ruzgys, Paulius, Satkauskas, Saulius, Kupcinskiene, Eugenija, Franke, Sabine, Thon, Cosima, Link, Alexander, Kupcinskas, Juozas, Skieceviciene, Jurgita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038213/
https://www.ncbi.nlm.nih.gov/pubmed/32013265
http://dx.doi.org/10.3390/ijms21030877
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author Streleckiene, Greta
Inciuraite, Ruta
Juzenas, Simonas
Salteniene, Violeta
Steponaitiene, Ruta
Gyvyte, Ugne
Kiudelis, Gediminas
Leja, Marcis
Ruzgys, Paulius
Satkauskas, Saulius
Kupcinskiene, Eugenija
Franke, Sabine
Thon, Cosima
Link, Alexander
Kupcinskas, Juozas
Skieceviciene, Jurgita
author_facet Streleckiene, Greta
Inciuraite, Ruta
Juzenas, Simonas
Salteniene, Violeta
Steponaitiene, Ruta
Gyvyte, Ugne
Kiudelis, Gediminas
Leja, Marcis
Ruzgys, Paulius
Satkauskas, Saulius
Kupcinskiene, Eugenija
Franke, Sabine
Thon, Cosima
Link, Alexander
Kupcinskas, Juozas
Skieceviciene, Jurgita
author_sort Streleckiene, Greta
collection PubMed
description Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as tumor-suppressors or oncogenes, playing an essential role in a variety of fundamental biological processes. In order to understand the functional relevance of miRNA dysregulation, studies analyzing their target genes are of major importance. Here, we chose to analyze two miRNAs, miR-20b and miR-451a, shown to be deregulated in many different malignancies, including GC. Deregulated expression of miR-20b and miR-451a was determined in GC cell lines and the INS-GAS mouse model. Using Western Blot and luciferase reporter assay we determined that miR-20b directly regulates expression of PTEN and TXNIP, and miR-451a: CAV1 and TSC1. Loss-of-function experiments revealed that down-regulation of miR-20b and up-regulation of miR-451a expression exhibits an anti-tumor effect in vitro (miR-20b: reduced viability, colony formation, increased apoptosis rate, and miR-451a: reduced colony forming ability). To summarize, the present study identified that expression of miR-20b and miR-451a are deregulated in vitro and in vivo and have a tumor suppressive role in GC through regulation of the PI3K/AKT/mTOR signaling pathway.
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spelling pubmed-70382132020-03-09 miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model Streleckiene, Greta Inciuraite, Ruta Juzenas, Simonas Salteniene, Violeta Steponaitiene, Ruta Gyvyte, Ugne Kiudelis, Gediminas Leja, Marcis Ruzgys, Paulius Satkauskas, Saulius Kupcinskiene, Eugenija Franke, Sabine Thon, Cosima Link, Alexander Kupcinskas, Juozas Skieceviciene, Jurgita Int J Mol Sci Article Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as tumor-suppressors or oncogenes, playing an essential role in a variety of fundamental biological processes. In order to understand the functional relevance of miRNA dysregulation, studies analyzing their target genes are of major importance. Here, we chose to analyze two miRNAs, miR-20b and miR-451a, shown to be deregulated in many different malignancies, including GC. Deregulated expression of miR-20b and miR-451a was determined in GC cell lines and the INS-GAS mouse model. Using Western Blot and luciferase reporter assay we determined that miR-20b directly regulates expression of PTEN and TXNIP, and miR-451a: CAV1 and TSC1. Loss-of-function experiments revealed that down-regulation of miR-20b and up-regulation of miR-451a expression exhibits an anti-tumor effect in vitro (miR-20b: reduced viability, colony formation, increased apoptosis rate, and miR-451a: reduced colony forming ability). To summarize, the present study identified that expression of miR-20b and miR-451a are deregulated in vitro and in vivo and have a tumor suppressive role in GC through regulation of the PI3K/AKT/mTOR signaling pathway. MDPI 2020-01-29 /pmc/articles/PMC7038213/ /pubmed/32013265 http://dx.doi.org/10.3390/ijms21030877 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Streleckiene, Greta
Inciuraite, Ruta
Juzenas, Simonas
Salteniene, Violeta
Steponaitiene, Ruta
Gyvyte, Ugne
Kiudelis, Gediminas
Leja, Marcis
Ruzgys, Paulius
Satkauskas, Saulius
Kupcinskiene, Eugenija
Franke, Sabine
Thon, Cosima
Link, Alexander
Kupcinskas, Juozas
Skieceviciene, Jurgita
miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model
title miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model
title_full miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model
title_fullStr miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model
title_full_unstemmed miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model
title_short miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model
title_sort mir-20b and mir-451a are involved in gastric carcinogenesis through the pi3k/akt/mtor signaling pathway: data from gastric cancer patients, cell lines and ins-gas mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038213/
https://www.ncbi.nlm.nih.gov/pubmed/32013265
http://dx.doi.org/10.3390/ijms21030877
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