tailieunhanh - Báo cáo khoa học: MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells

MicroRNAs are aberrantly expressed in cancer; microRNA-143 (miR-143) is down-regulated in colon cancer. HCT116 human colorectal cancer cells were used to investigate the biological role of miR-143. Transient miR-143 overexpression resulted in an approximate 60% reduction in cell via-bility. | MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells Pedro M. Borralho1 Betsy T. Kren2 Rui E. Castro1 Isabel B. Moreira da Silva1 Clifford J. Steer2 3 and Cecilia M. P. Rodrigues1 1 Research Institute for Medicines and PharmaceuticalSciences Faculty of Pharmacy University of Lisbon Portugal 2 Department of Medicine University of Minnesota Medical School Minneapolis MN USA 3 Department of Genetics CellBiology and Development University of Minnesota Medical School Minneapolis MN USA Keywords 5-fluorouracil apoptosis chemosensitizer ERK5 miR-143 Correspondence C. M. P. Rodrigues Research Institute for Medicines and Pharmaceutical Sciences Faculty of Pharmacy University of Lisbon Avenida Professor Gama Pinto 1649-003 Lisbon Portugal Fax 351 21 794 6491 Tel 351 21 794 6400 E-mail cmprodrigues@ Received 29 April 2009 revised 2 August 2009 accepted 15 September 2009 doi MicroRNAs are aberrantly expressed in cancer microRNA-143 miR-143 is down-regulated in colon cancer. HCT116 human colorectal cancer cells were used to investigate the biological role of miR-143. Transient miR-143 overexpression resulted in an approximate 60 reduction in cell viability. In addition stable miR-143 overexpressing cells were selected with G418 and exposed to 5-fluorouracil. Increased stable expression of miR-143 was associated with decreased viability and increased cell death after exposure to 5-fluorouracil. These changes were associated with increased nuclear fragmentation and caspase -3 -8 and -9 activities. In addition extracellular-regulated protein kinase 5 nuclear factor-KB and Bcl-2 protein expression was down-regulated by miR-143 and further reduced by exposure to 5-fluorouracil. In conclusion miR-143 modulates the expression of key proteins involved in the regulation of cell proliferation death and chemotherapy response. In addition miR-143 increases the sensitivity of colon cancer

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