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- Title
MicroRNA-143 reduces viability and increases sensitivity to 5-fluorouracil in HCT116 human colorectal cancer cells.
- Authors
Borralho, Pedro M; Kren, Betsy T; Castro, Rui E; da Silva, Isabel B Moreira; Steer, Clifford J; Rodrigues, Cecília M P
- 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-kappaB 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-kappaB 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.
- Publication
The FEBS journal, 2009, Vol 276, Issue 22, p6689
- ISSN
1742-4658
- Publication type
Journal Article
- DOI
10.1111/j.1742-4658.2009.07383.x