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

被引：11

作者：

Babaei-Jadidi, Roya ^{[1
,2
]}

Kashfi, Hossein ^{[1
,3
]}

Alelwani, Walla ^{[4
]}

Bakhtiari, Ashkan Karimi ^{[1
]}

Kattan, Shahad W. ^{[1
,5
]}

Mansouri, Omniah A. ^{[6
]}

Mukherjee, Abhik ^{[7
]}

Lobo, Dileep N. ^{[8
,9
]}

Nateri, Abdolrahman S. ^{[1
]}

机构：

[1] Univ Nottingham, Sch Med, Translat Med Sci Unit, BioDiscovery Inst,Canc Genet & Stem Cell Grp, Nottingham NG7 2UH, England

[2] Univ Nottingham, Sch Med, Resp Med, Nottingham NG7 2UH, England

[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL USA

[4] Univ Jeddah, Coll Sci, Dept Biochem, Jeddah, Saudi Arabia

[5] Taibah Univ, Coll Appl Med Sci, Med Lab Dept, Yanbu, Saudi Arabia

[6] Univ Jeddah, Coll Sci, Dept Biol, Jeddah 21959, Saudi Arabia

[7] Univ Nottingham, Sch Med, BioDiscovery Inst, Histopathol, Nottingham NG7 2UH, England

[8] Nottingham Univ Hosp NHS Trust, Nottingham Biomed Res Ctr, Natl Inst Hlth Res, Natl Nottingham Digest Dis Ctr,Nottingham Digest, Nottingham, England

[9] Univ Nottingham, Queens Med Ctr, Sch Life Sci, MRC Versus Arthrit Ctr Musculoskeletal Ageing Res, Nottingham, England

来源：

ONCOGENESIS | 2022年 / 11卷 / 01期

基金：

英国医学研究理事会;

关键词：

ADULT STEM-CELLS; COLORECTAL-CANCER; F-BOX; SMALL-INTESTINE; BREAST-CANCER; UP-REGULATION; MICRORNA; 135; MOUSE MODEL; EXPRESSION; SPOCK1;

D O I：

10.1038/s41389-021-00376-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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( increment 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.

引用

页数：12

共 100 条

[41] Fbxw7-associated drug resistance is reversed by induction of terminal differentiation in murine intestinal organoid culture [J].