MicroRNAs (
miRNAs) have recently taken center stage in the field of human molecular oncology. Most of the chemotherapeutics are able to interfere with
nucleic acid metabolism and gene expression. The purpose of this study was to determine how
5-fluorouracil (5-FU) and
oxaliplatin (L-OHP) modify the expression profiles of
miRNAs in HCT-8 and HCT-116
colon cancer cells and whether the pharmacodynamic mechanisms of the chemotherapeutics could rely in part on their influence on
miRNA expression. The expression profiles of
miRNAs were determined using a
miRNA microarray containing 856 human
miRNA probes. The expression of selected
miRNAs was then validated by real-time RT-PCR. Fifty-six up- and 50 down-regulations of
miRNA expression with statistical significance were identified in
colon cancer cells following exposure to
5-FU or L-OHP compared to matched control cells. The down-regulations of miR-197, miR-191, miR-92a, miR-93, miR-222 and miR-1826, whose expression was significantly down-regulated in both cell lines after the treatment of one drug or in one cell line following exposure to either drug, were further validated. Analysis of the relevant literature indicated that, in line with the
tumor suppressive activity of
5-FU and L-OHP, the six down-regulated
miRNAs might function as oncogenes due to their overexpression in
cancers, and some of them correlated with the poor prognosis and treatment-resistance of
cancer. In conclusion, we identify the modification of
miRNA expression profiles in
colon cancer cells following exposure to
5-FU and L-OHP, and our results indicate that their pharmacodynamic mechanisms could rely in part on their influence on the down-regulated
miRNA expression. Further studies are needed to determine whether these
miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference.