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

Pedro M. Borralho, Betsy T. Kren, Rui E. Castro, Isabel B. Moreira Da Silva, Clifford J. Steer, Cecília M.P. Rodrigues

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6689-6700
Number of pages12
JournalFEBS Journal
Volume276
Issue number22
DOIs
StatePublished - Nov 2009

Keywords

  • 5-fluorouracil
  • Apoptosis
  • Chemosensitizer
  • ERK5
  • MiR-143

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