Abstract
Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan® miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-α, IL-1β, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1α were increased, and IFN-γ expression was decreased after radiation, whereas, IL-6, IFN-γ, TNF-α, IL-1β, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1α were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.
Highlights
Colorectal cancers (CRCs) are the third most common type of cancer, with approximately one million new cases each year world-wide, and the second most frequent cause of cancer-related death in the United States and in Europe [1]
The present study aimed to investigate the p53 gene mediated expression of miRNAs, cyto- and chemokines in human colon cancer cells (HCT116) after the treatments of radiation and SN38, and further examined the most significantly up- or down-regulated miRNAs to find out whether there is any possible interaction between these miRNAs and increased or decreased cyto- and chemokine expression in colon cancer cells in response to the radiation and SN38 treatments
Increasing dose (2Gy-10Gy) of radiation was used to test the cellular viability of HCT116p53+/+, HCT116p53+/- and HCT116p53-/, and 2Gy radiation is used as an ID50 value for all the subsequent experiments
Summary
Colorectal cancers (CRCs) are the third most common type of cancer, with approximately one million new cases each year world-wide, and the second most frequent cause of cancer-related death in the United States and in Europe [1] It is the second most common site-specific cancer affecting both men and women. The identification of molecular biomarkers and other therapeutic target has been the focus of extensive research where the ultimate goal is to discover markers with a diagnostic and/or therapeutic value In most cases, it is not clear what causes colon cancer, several risk factors have been identified www.impactjournals.com/oncotarget over the years. Each miRNA has the ability to control the activity of hundreds of target genes, including oncogenes and tumor suppressors, like p53 [14], miRNA expression in relation to radiation, SN38, and increase or decrease of cyto- or chemokine expression is less investigated
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