IngentaConnect MicroRNA-143 reduces viability and increases sensitivity to 5-flu...

Authors: Borralho, Pedro M.¹; Kren, Betsy T.²; Castro, Rui E.¹; Moreira da Silva, Isabel B.¹; Steer, Clifford J.; Rodrigues, Cecília M. P.¹

Source: FEBS Journal, Volume 276, Number 22, November 2009 , pp. 6689-6700(12)

Publisher: Blackwell Publishing

Abstract:

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-κB 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 cells to 5-fluorouracil, probably acting through extracellular-regulated protein kinase 5/nuclear factor-κB regulated pathways. Collectively, the data obtained in the present study suggest anti-proliferative, chemosensitizer and putative pro-apoptotic roles for miR-143 in colon cancer.

Keywords: 5-fluorouracil; apoptosis; chemosensitizer; ERK5; miR-143

Document Type: Research article

DOI: 10.1111/j.1742-4658.2009.07383.x

Affiliations: 1: Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Portugal 2: Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA

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MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells