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.

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: Springer Science and Business Media LLC
• 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/