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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; Bakhtiari, Ashkan; Kattan, Shahad W; Mansouri, Omniah A; Mukherjee, Abhik; Lobo, Dileep N.; Nateri, Abdolrahman S.

Authors

Hossein Kashfi

Walla Alelwani

Ashkan Bakhtiari

Shahad W Kattan

Omniah A Mansouri

DILEEP LOBO dileep.lobo@nottingham.ac.uk
Professor of Gastrointestinal Surgery



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 ApcMinFbxw7∆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.

Citation

Babaei-Jadidi, R., Kashfi, H., Alelwani, W., Bakhtiari, A., Kattan, S. W., Mansouri, O. A., …Nateri, A. S. (2022). Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids. Oncogenesis, 11, Article 4. https://doi.org/10.1038/s41389-021-00376-1

Journal Article Type Article
Acceptance Date Dec 17, 2021
Online Publication Date Jan 19, 2022
Publication Date Jan 19, 2022
Deposit Date Dec 21, 2021
Publicly Available Date Jan 19, 2022
Journal Oncogenesis
Electronic ISSN 2157-9024
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 11
Article Number 4
DOI https://doi.org/10.1038/s41389-021-00376-1
Keywords Cancer Research; Molecular Biology
Public URL https://nottingham-repository.worktribe.com/output/7053817
Publisher URL https://www.nature.com/articles/s41389-021-00376-1
Related Public URLs https://www.nature.com/oncsis/

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