Drug resistance of colon cancer cells to 5-fluorouracil mediated by microRNA-21.
10.3760/cma.j.issn.1003-9406.2015.05.003
- Author:
Liyuan WU
1
;
Si LI
;
Rui PENG
;
Shu GONG
;
Liu XU
;
Fangdong ZOU
Author Information
1. College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, P. R. China. Email: zxuliu@163.com.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family G, Member 5;
ATP-Binding Cassette Transporters;
genetics;
Antimetabolites, Antineoplastic;
pharmacology;
Apoptosis Regulatory Proteins;
physiology;
Cell Line, Tumor;
Colonic Neoplasms;
drug therapy;
pathology;
Drug Resistance, Neoplasm;
Fluorouracil;
pharmacology;
Humans;
Hyaluronan Receptors;
genetics;
Lipoproteins;
genetics;
MicroRNAs;
physiology;
RNA-Binding Proteins;
physiology
- From:
Chinese Journal of Medical Genetics
2015;32(5):620-624
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore downstream regulatory pathway of microRNA-21 (miR-21) in colon cancer cells (RKO) through detecting miR-21 and its target PDCD4, and the influence of miR-21 regulation on the sensitivity of RKO cells to 5-fluorouracil (5-FU). METHODS 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the effect of 5-FU on the viability of RKO cells with knockout of miR-21 or high expression of PDCD4. Real-time was used to determine the expression of PDCD4, ABCC5 and CD44 in RKO cell after knockout of miR-21. RESULTS MTT assay reveals that the IC50 of 5-FU in RKO-WT cells (52.82 ± 0.06 umol/L) was about 67% higher than in miR-21 knockout cells (32.23 ± 0.05 umol/L) (P < 0.05), and the apoptosis ratio elevated after knockout of miR-21. High expression of PDCD4, a target gene of miR-21, can negatively regulate the expression of ABC transporter ABCC5 and the stem cell marker CD44. CONCLUSION MiR-21 can mediate the drug resistance to 5-FU by inhibiting its target PDCD4, which can regulate the expression of ABCC5 and CD44 genes.
