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Cellular Oncology
Published in: Cellular Oncology 1/2016

01-02-2016 | Original Paper

miR-101-2, miR-125b-2 and miR-451a act as potential tumor suppressors in gastric cancer through regulation of the PI3K/AKT/mTOR pathway

Authors: Ismael Riquelme, Oscar Tapia, Pamela Leal, Alejandra Sandoval, Matthew G. Varga, Pablo Letelier, Kurt Buchegger, Carolina Bizama, Jaime A. Espinoza, Richard M. Peek, Juan Carlos Araya, Juan Carlos Roa

Published in: Cellular Oncology | Issue 1/2016

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Abstract

Background

Gastric cancer (GC) is a deadly malignancy worldwide. In the past, it has been shown that cellular signaling pathway alterations play a crucial role in the development of GC. In particular, deregulation of the PI3K/AKT/mTOR pathway seems to affect multiple GC functions including growth, proliferation, metabolism, motility and angiogenesis. Targeting alterations in this pathway by microRNAs (miRNAs) represents a potential therapeutic strategy, especially in inhibitor-resistant tumors. The objective of this study was to evaluate the expression of 3 pre-selected miRNAs, miR-101-2, miR-125b-2 and miR-451a, in a series of primary GC tissues and matched non-GC tissues and in several GC-derived cell lines, and to subsequently evaluate the functional role of these miRNAs.

Methods

Twenty-five primary GC samples, 25 matched non-GC samples and 3 GC-derived cell lines, i.e., AGS, MKN28 and MKN45, were included in this study. miRNA and target gene expression levels were assessed by quantitative RT-PCR and western blotting, respectively. Subsequently, cell viability, clone formation, cell death, migration and invasion assays were performed on AGS cells.

Results

miR-101-2, miR-125b-2 and miR-451a were found to be down-regulated in the primary GC tissues and the GC-derived cell lines tested. MiRNA mimic transfections significantly reduced cell viability and colony formation, increased cell death and reduced cell migration and invasion in AGS cells. We also found that exogenous expression of miR-101-2, miR-125b-2 and miR-451a decreased the expression of their putative targets MTOR, PIK3CB and TSC1, respectively.

Conclusions

Our expression analyses and in vitro functional assays suggest that miR-101-2, miR-125b-2 and miR-451a act as potential tumor suppressors in primary GCs as well as in GC-derived AGS cells.
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Metadata
Title
miR-101-2, miR-125b-2 and miR-451a act as potential tumor suppressors in gastric cancer through regulation of the PI3K/AKT/mTOR pathway
Authors
Ismael Riquelme
Oscar Tapia
Pamela Leal
Alejandra Sandoval
Matthew G. Varga
Pablo Letelier
Kurt Buchegger
Carolina Bizama
Jaime A. Espinoza
Richard M. Peek
Juan Carlos Araya
Juan Carlos Roa
Publication date
01-02-2016
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 1/2016
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-015-0247-3

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