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microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer
MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the los...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978802/ https://www.ncbi.nlm.nih.gov/pubmed/29527004 http://dx.doi.org/10.1038/s41388-018-0124-4 |
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author | Kim, Sinae Lee, Eunji Jung, Jaeyun Lee, Jong Won Kim, Hee Jung Kim, Jisun Yoo, Hyun ju Lee, Hee Jin Chae, Sun Young Jeon, Sang Min Son, Byung Ho Gong, Gyungyup Sharan, Shyam K Chang, Suhwan |
author_facet | Kim, Sinae Lee, Eunji Jung, Jaeyun Lee, Jong Won Kim, Hee Jung Kim, Jisun Yoo, Hyun ju Lee, Hee Jin Chae, Sun Young Jeon, Sang Min Son, Byung Ho Gong, Gyungyup Sharan, Shyam K Chang, Suhwan |
author_sort | Kim, Sinae |
collection | PubMed |
description | MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer. |
format | Online Article Text |
id | pubmed-5978802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59788022018-06-04 microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer Kim, Sinae Lee, Eunji Jung, Jaeyun Lee, Jong Won Kim, Hee Jung Kim, Jisun Yoo, Hyun ju Lee, Hee Jin Chae, Sun Young Jeon, Sang Min Son, Byung Ho Gong, Gyungyup Sharan, Shyam K Chang, Suhwan Oncogene Article MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer. Nature Publishing Group UK 2018-03-12 2018 /pmc/articles/PMC5978802/ /pubmed/29527004 http://dx.doi.org/10.1038/s41388-018-0124-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Article Kim, Sinae Lee, Eunji Jung, Jaeyun Lee, Jong Won Kim, Hee Jung Kim, Jisun Yoo, Hyun ju Lee, Hee Jin Chae, Sun Young Jeon, Sang Min Son, Byung Ho Gong, Gyungyup Sharan, Shyam K Chang, Suhwan microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer |
title | microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer |
title_full | microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer |
title_fullStr | microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer |
title_full_unstemmed | microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer |
title_short | microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer |
title_sort | microrna-155 positively regulates glucose metabolism via pik3r1-foxo3a-cmyc axis in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978802/ https://www.ncbi.nlm.nih.gov/pubmed/29527004 http://dx.doi.org/10.1038/s41388-018-0124-4 |
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