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

Roya Babaei-Jadidi; Hossein Kashfi; Walla Alelwani; Ashkan Karimi Bakhtiari; Shahad W. Kattan; Omniah A. Mansouri; Abhik Mukherjee; Dileep N. Lobo; Abdolrahman S. Nateri

doi:10.1038/s41389-021-00376-1

Oncogenesis (Jan 2022)

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

Roya Babaei-Jadidi,
Hossein Kashfi,
Walla Alelwani,
Ashkan Karimi Bakhtiari,
Shahad W. Kattan,
Omniah A. Mansouri,
Abhik Mukherjee,
Dileep N. Lobo,
Abdolrahman S. Nateri

Affiliations

Roya Babaei-Jadidi: Cancer Genetics & Stem Cell Group, BioDiscovery Institute, Translational Medical Sciences Unit, School of Medicine, University of Nottingham
Hossein Kashfi: Cancer Genetics & Stem Cell Group, BioDiscovery Institute, Translational Medical Sciences Unit, School of Medicine, University of Nottingham
Walla Alelwani: Department of Biochemistry, College of Science, University of Jeddah
Ashkan Karimi Bakhtiari: Cancer Genetics & Stem Cell Group, BioDiscovery Institute, Translational Medical Sciences Unit, School of Medicine, University of Nottingham
Shahad W. Kattan: Cancer Genetics & Stem Cell Group, BioDiscovery Institute, Translational Medical Sciences Unit, School of Medicine, University of Nottingham
Omniah A. Mansouri: Department of Biology, University of Jeddah, College of Science
Abhik Mukherjee: Histopathology, BioDiscovery Institute, School of Medicine, University of Nottingham, NG7 2UH
Dileep N. Lobo: Nottingham Digestive Diseases Centre, National Nottingham Digestive Diseases Centre, National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham
Abdolrahman S. Nateri: Cancer Genetics & Stem Cell Group, BioDiscovery Institute, Translational Medical Sciences Unit, School of Medicine, University of Nottingham

DOI: https://doi.org/10.1038/s41389-021-00376-1
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 12

Abstract

Read online

Abstract 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.

Published in Oncogenesis

ISSN: 2157-9024 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.nature.com/oncsis/index.html

About the journal