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MicroRNA‐143 reduces viability and increases sensitivity to 5‐fluorouracil in HCT116 human colorectal cancer cells
Author(s) -
Borralho Pedro M.,
Kren Betsy T.,
Castro Rui E.,
Moreira da Silva Isabel B.,
Steer Clifford J.,
Rodrigues Cecília M. P.
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07383.x
Subject(s) - viability assay , colorectal cancer , microrna , apoptosis , cancer research , programmed cell death , biology , cancer cell , cancer , chemistry , microbiology and biotechnology , biochemistry , genetics , gene
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.