Ismael Riquelme1, Oscar Tapia1, Pamela Leal2, Alejandra Sandoval1, Matthew G Varga3, Pablo Letelier4, Kurt Buchegger1, Carolina Bizama5, Jaime A Espinoza5, Richard M Peek3, Juan Carlos Araya6, Juan Carlos Roa5. 1. Laboratory of Molecular Pathology, Pathology Department, School of Medicine, BIOREN-CEGIN, Universidad de La Frontera, Avenida Alemania 0458, 4810296 Temuco, Chile. 2. Molecular Biology and Biomedicine Lab, CEGIN-BIOREN, Universidad de La Frontera, Avenida Alemania 0458, 4810296 Temuco, Chile. 3. Division of Gastroenterology, Departments of Medicine and Cancer Biology, Vanderbilt University School of Medicine, 2215 Garland Avenue Nashville, 37232 Nashville, TN, USA. 4. School of Health Sciences, Universidad Catolica de Temuco, Manuel Montt 56, 4813302 Temuco, Chile. 5. Department of Pathology, UC Centre for Investigational Oncology (CITO), Advanced Centre for Chronic Diseases (ACCDiS), School of Medicine, Pontificia Universidad Catolica de Chile, Marcoleta 377, 7th Floor, 8330024 Santiago, Chile. 6. Department of Pathology, School of Medicine, Universidad de La Frontera, Avenida Alemania 0458, 4810296 Temuco, Chile.
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.
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.
Authors: Ahmedin Jemal; Freddie Bray; Melissa M Center; Jacques Ferlay; Elizabeth Ward; David Forman Journal: CA Cancer J Clin Date: 2011-02-04 Impact factor: 508.702
Authors: Bryan J Dicken; David L Bigam; Carol Cass; John R Mackey; Anil A Joy; Stewart M Hamilton Journal: Ann Surg Date: 2005-01 Impact factor: 12.969
Authors: C Chang; J Liu; W He; M Qu; X Huang; Y Deng; L Shen; X Zhao; H Guo; J Jiang; X Y Fu; R Huang; D Zhang; J Yan Journal: Oncogene Date: 2017-10-02 Impact factor: 9.867