Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids.
Roya Babaei-JadidiHossein KashfiWalla AlelwaniAshkan Karimi BakhtiariShahad W KattanOmniah A MansouriAbhik MukherjeeDileep N LoboAbdolrahman S NateriPublished in: Oncogenesis (2022)
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.
Keyphrases
- poor prognosis
- cancer therapy
- cell proliferation
- long non coding rna
- mouse model
- drug delivery
- binding protein
- photodynamic therapy
- signaling pathway
- single cell
- transcription factor
- genome wide
- emergency department
- squamous cell carcinoma
- type diabetes
- long noncoding rna
- gene expression
- adipose tissue
- dna methylation
- insulin resistance
- blood glucose
- bioinformatics analysis
- smoking cessation
- rectal cancer
- genome wide analysis
- wild type