Wei-Hua Dong1, Qin Li1, Xiao-Yan Zhang1, Qing Guo1, Huizheng Li1, Tian-Yun Wang1. 1. Department of Biochemistry and Molecular Biology, Xinxiang Medical University Henan 453003 China ; Henan Collaborative Innovation Canter of Molecular Diagnosis and Laboratory Medicine Xinxiang, 453003, Henan, China.
Abstract
BACKGROUND: Vincristine (VCR) is a chemical that is widely used in tumor therapy. While long-term use can make tumor cells resistant to VCR, the underlying mechanisms of this resistance are still unclear. OBJECTIVE: This study aimed at investigating the role of microRNA (miRNA) in colon cancer drug resistance. METHODS: HCT-8 colon carcinoma cells were cultured and treated with different VCR concentrations to establish an HCT-8/VCR resistant cell line. Whole-genome screens, HiSeq 2500 sequencing, and bioinformatics methods were used to detect and analyze differences in miRNA expression between the drug-resistant HCT-8/VCR cells and non-resistant HCT-8 cells. Differential expression profiles of miRNAs were constructed based on sequencing result. RESULTS: The HCT-8/VCR resistant colon carcinoma cell line was established. With regard to the difference in drug resistance between HCT-8/VCR and HCT-8 cells, 24 miRNAs showed statistically significant differences in their expression (fold change > 4), of which 17 were up-regulated. Seven miRNAs were down-regulated. CONCLUSION: As abnormal expression of miRNAs was associated with VCR resistance of colon carcinoma cells, differences in miRNA expression may play a key role in VCR resistance of colon cancer cells.
BACKGROUND:Vincristine (VCR) is a chemical that is widely used in tumor therapy. While long-term use can make tumor cells resistant to VCR, the underlying mechanisms of this resistance are still unclear. OBJECTIVE: This study aimed at investigating the role of microRNA (miRNA) in colon cancer drug resistance. METHODS: HCT-8 colon carcinoma cells were cultured and treated with different VCR concentrations to establish an HCT-8/VCR resistant cell line. Whole-genome screens, HiSeq 2500 sequencing, and bioinformatics methods were used to detect and analyze differences in miRNA expression between the drug-resistant HCT-8/VCR cells and non-resistant HCT-8 cells. Differential expression profiles of miRNAs were constructed based on sequencing result. RESULTS: The HCT-8/VCR resistant colon carcinoma cell line was established. With regard to the difference in drug resistance between HCT-8/VCR and HCT-8 cells, 24 miRNAs showed statistically significant differences in their expression (fold change > 4), of which 17 were up-regulated. Seven miRNAs were down-regulated. CONCLUSION: As abnormal expression of miRNAs was associated with VCR resistance of colon carcinoma cells, differences in miRNA expression may play a key role in VCR resistance of colon cancer cells.
Entities:
Keywords:
Colon cancer; HCT-8; drug resistance; microRNA
Authors: Jun Lu; Gad Getz; Eric A Miska; Ezequiel Alvarez-Saavedra; Justin Lamb; David Peck; Alejandro Sweet-Cordero; Benjamin L Ebert; Raymond H Mak; Adolfo A Ferrando; James R Downing; Tyler Jacks; H Robert Horvitz; Todd R Golub Journal: Nature Date: 2005-06-09 Impact factor: 49.962