ROYA BABAEI-JADIDI Roya.Babaei-jadidi@nottingham.ac.uk
Research Fellow
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
Dr ABHIK MUKHERJEE ABHIK.MUKHERJEE1@NOTTINGHAM.AC.UK
Clinical Associate Professor
DILEEP LOBO dileep.lobo@nottingham.ac.uk
Professor of Gastrointestinal Surgery
ABDOLRAHMAN SHAMS-NATERI a.nateri@nottingham.ac.uk
Associate Professor
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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Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids
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