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The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5

BACKGROUND: The role of microRNA (miRNA) in modulating the function of cancer stem cells through diverse signaling pathway has been evidenced. We here identified a role of microRNA (miRNA) family, specifically miR-148/152, in gastric cancer and delineated its functional effects on gastric cancer ste...

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Autores principales: Li, Xiaoying, Li, Lin, Wu, Jiangying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912648/
https://www.ncbi.nlm.nih.gov/pubmed/36765401
http://dx.doi.org/10.1186/s12967-023-03894-1
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author Li, Xiaoying
Li, Lin
Wu, Jiangying
author_facet Li, Xiaoying
Li, Lin
Wu, Jiangying
author_sort Li, Xiaoying
collection PubMed
description BACKGROUND: The role of microRNA (miRNA) in modulating the function of cancer stem cells through diverse signaling pathway has been evidenced. We here identified a role of microRNA (miRNA) family, specifically miR-148/152, in gastric cancer and delineated its functional effects on gastric cancer stem cells. METHODS: Bioinformatics analysis was conducted to analyze expression of integrin α5 (ITGA5) which was verified through expression determination in clinical tissue samples. Next, the upstream regulatory factors of ITGA5 were determined. CD44(+)EpCAM (high) cells sorted from AGS cells subjected to gain-of-function experiments, followed by evaluation of their capacity of colony formation, generation of tumorosphere, cell migration and viability in vitro and xenograft tumor formation in vivo. RESULTS: ITGA5 was elevated in gastric cancer tissues and confirmed as a target gene of the miR-148/152 family members. The miR-148/152 family members were downregulated in gastric cancer tissues and cells. Decreased expression of miR-148/152 family members was also detected in gastric cancer stem cells. However, the raised expression led to reduced colony formation, tumorosphere, cell migration, cell viability, and drug resistance of CD44+EpCAM (high) AGS cells in vitro, and tumorigenesis in vitro. ITGA5 overexpression reversed the effect of the miR-148/152 family members. CONCLUSIONS: This study demonstrates that the miR-148/152 family members may prevent gastric cancer stem cell-like properties by targeting ITGA5, which can serve as an appealing target for gastric cancer treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-03894-1.
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spelling pubmed-99126482023-02-11 The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5 Li, Xiaoying Li, Lin Wu, Jiangying J Transl Med Research BACKGROUND: The role of microRNA (miRNA) in modulating the function of cancer stem cells through diverse signaling pathway has been evidenced. We here identified a role of microRNA (miRNA) family, specifically miR-148/152, in gastric cancer and delineated its functional effects on gastric cancer stem cells. METHODS: Bioinformatics analysis was conducted to analyze expression of integrin α5 (ITGA5) which was verified through expression determination in clinical tissue samples. Next, the upstream regulatory factors of ITGA5 were determined. CD44(+)EpCAM (high) cells sorted from AGS cells subjected to gain-of-function experiments, followed by evaluation of their capacity of colony formation, generation of tumorosphere, cell migration and viability in vitro and xenograft tumor formation in vivo. RESULTS: ITGA5 was elevated in gastric cancer tissues and confirmed as a target gene of the miR-148/152 family members. The miR-148/152 family members were downregulated in gastric cancer tissues and cells. Decreased expression of miR-148/152 family members was also detected in gastric cancer stem cells. However, the raised expression led to reduced colony formation, tumorosphere, cell migration, cell viability, and drug resistance of CD44+EpCAM (high) AGS cells in vitro, and tumorigenesis in vitro. ITGA5 overexpression reversed the effect of the miR-148/152 family members. CONCLUSIONS: This study demonstrates that the miR-148/152 family members may prevent gastric cancer stem cell-like properties by targeting ITGA5, which can serve as an appealing target for gastric cancer treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-03894-1. BioMed Central 2023-02-10 /pmc/articles/PMC9912648/ /pubmed/36765401 http://dx.doi.org/10.1186/s12967-023-03894-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Xiaoying
Li, Lin
Wu, Jiangying
The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
title The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
title_full The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
title_fullStr The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
title_full_unstemmed The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
title_short The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
title_sort members of the mir-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of itga5
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912648/
https://www.ncbi.nlm.nih.gov/pubmed/36765401
http://dx.doi.org/10.1186/s12967-023-03894-1
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