5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro

Abstract

Abstract. 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.

miR-191: an emerging player in disease biology

“…Work in our lab shows that miR-191 overexpressing breast cancer cells show increased survival in response to chemotherapeutic drug or hypoxia treatment (Nagpal et al, 2013). Altogether these reports suggest prospects of miR-191 being a target for studying chemotherapeutic interference (Zhou et al, 2010). …”

“…Chaudhry et al (2013) have shown miR-191 induction in response to X-ray treatment in human lymphoblast cells (TK6 cell line). However, miR-191 was shown to be rather downregulated in two colon cancer cell lines HCT116 and HCT-8 when treated with chemotherapeutic drugs (5-Fluorouracil and Oxaliplatin; Zhou et al, 2010). Thus, the effects on miR-191 levels may vary depending on the stress or tissue/cell type.…”

CELF Family Proteins in Cancer: Highlights on the RNA-Binding Protein/Noncoding RNA Regulatory Axis

“…Cisplatin Downregulated Ovarian cancer cell lines [165] Suberoylanilide hydroxamic acid Downregulated Human lung carcinoma cell line [166] 5-Fluorouracil Downregulated Colon cancer cell line [167] Bicalutamide Downregulated Prostate cancer cell line [168] miR-107 5-Fluorouracil Upregulated Breast cancer cells [163] Anthranilamide-pyrazolo [1,5-a] pyrimidine Upregulated Neuroblastoma cell [169] miR-140 5-Fluorouracil Upregulated Breast cancer cells [163] miR-140-5p Suberoylanilide hydroxamic acid Upregulated Human lung carcinoma cell line [166] mir-155…”