title: [Drug resistance of colon cancer cells to 5-fluorouracil mediated by microRNA-21].
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.
authors.affiliation: College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, P. R. China. Email: zxuliu@163.com.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Wu
authors.forename: Si
authors.initials: S
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Peng
authors.forename: Shu
authors.initials: S
authors.lastname: Gong
authors.forename: Liu
authors.initials: L
authors.lastname: Xu
authors.forename: Fangdong
authors.initials: F
authors.lastname: Zou
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics; D008074:Lipoproteins / Q000235:genetics; D035683:MicroRNAs / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology
chemical_list: C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D008074:Lipoproteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D005472:Fluorouracil