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Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids

Little is known about the role of microRNAs (miRNAs) in rewiring the metabolism within tumours and adjacent non-tumour bearing normal tissue and their potential in cancer therapy. This study aimed to investigate the relationship between deregulated miRNAs and metabolic components in murine duodenal...

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Autores principales: Babaei-Jadidi, Roya, Kashfi, Hossein, Alelwani, Walla, Karimi Bakhtiari, Ashkan, Kattan, Shahad W., Mansouri, Omniah A., Mukherjee, Abhik, Lobo, Dileep N., Nateri, Abdolrahman S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770633/
https://www.ncbi.nlm.nih.gov/pubmed/35046388
http://dx.doi.org/10.1038/s41389-021-00376-1
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author Babaei-Jadidi, Roya
Kashfi, Hossein
Alelwani, Walla
Karimi Bakhtiari, Ashkan
Kattan, Shahad W.
Mansouri, Omniah A.
Mukherjee, Abhik
Lobo, Dileep N.
Nateri, Abdolrahman S.
author_facet Babaei-Jadidi, Roya
Kashfi, Hossein
Alelwani, Walla
Karimi Bakhtiari, Ashkan
Kattan, Shahad W.
Mansouri, Omniah A.
Mukherjee, Abhik
Lobo, Dileep N.
Nateri, Abdolrahman S.
author_sort Babaei-Jadidi, Roya
collection PubMed
description Little is known about the role of microRNAs (miRNAs) in rewiring the metabolism within tumours and adjacent non-tumour bearing normal tissue and their potential in cancer therapy. This study aimed to investigate the relationship between deregulated miRNAs and metabolic components in murine duodenal polyps and non-polyp-derived organoids (mPOs and mNPOs) from a double-mutant Apc(Min)Fbxw7(∆G) mouse model of intestinal/colorectal cancer (CRC). We analysed the expression of 373 miRNAs and 12 deregulated metabolic genes in mPOs and mNPOs. Our findings revealed miR-135b might target Spock1. Upregulation of SPOCK1 correlated with advanced stages of CRCs. Knockdown of miR-135b decreased the expression level of SPOCK1, glucose consumption and lactic secretion in CRC patient-derived tumours organoids (CRC tPDOs). Increased SPOCK1 induced by miR-135b overexpression promoted the Warburg effect and consequently antitumour effect of 5-fluorouracil. Thus, combination with miR-135b antisense nucleotides may represent a novel strategy to sensitise CRC to the chemo-reagent based treatment.
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spelling pubmed-87706332022-02-04 Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids Babaei-Jadidi, Roya Kashfi, Hossein Alelwani, Walla Karimi Bakhtiari, Ashkan Kattan, Shahad W. Mansouri, Omniah A. Mukherjee, Abhik Lobo, Dileep N. Nateri, Abdolrahman S. Oncogenesis Article Little is known about the role of microRNAs (miRNAs) in rewiring the metabolism within tumours and adjacent non-tumour bearing normal tissue and their potential in cancer therapy. This study aimed to investigate the relationship between deregulated miRNAs and metabolic components in murine duodenal polyps and non-polyp-derived organoids (mPOs and mNPOs) from a double-mutant Apc(Min)Fbxw7(∆G) mouse model of intestinal/colorectal cancer (CRC). We analysed the expression of 373 miRNAs and 12 deregulated metabolic genes in mPOs and mNPOs. Our findings revealed miR-135b might target Spock1. Upregulation of SPOCK1 correlated with advanced stages of CRCs. Knockdown of miR-135b decreased the expression level of SPOCK1, glucose consumption and lactic secretion in CRC patient-derived tumours organoids (CRC tPDOs). Increased SPOCK1 induced by miR-135b overexpression promoted the Warburg effect and consequently antitumour effect of 5-fluorouracil. Thus, combination with miR-135b antisense nucleotides may represent a novel strategy to sensitise CRC to the chemo-reagent based treatment. Nature Publishing Group UK 2022-01-19 /pmc/articles/PMC8770633/ /pubmed/35046388 http://dx.doi.org/10.1038/s41389-021-00376-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. 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/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Babaei-Jadidi, Roya
Kashfi, Hossein
Alelwani, Walla
Karimi Bakhtiari, Ashkan
Kattan, Shahad W.
Mansouri, Omniah A.
Mukherjee, Abhik
Lobo, Dileep N.
Nateri, Abdolrahman S.
Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
title Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
title_full Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
title_fullStr Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
title_full_unstemmed Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
title_short Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
title_sort anti-mir-135/spock1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770633/
https://www.ncbi.nlm.nih.gov/pubmed/35046388
http://dx.doi.org/10.1038/s41389-021-00376-1
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