Abstract
Inositol hexaphosphate (IP6), a natural dietary component, has been found as an antitumor agent by stimulating apoptosis and inhibiting cancer cell proliferation, their migration, and metastasis in diverse cancers including colon cancer. However, molecular mechanisms of its action have not been well understood. In recent years, microRNAs (miRNAs) have been reported to play important roles in a broad range of biologic processes, such as cell growth, proliferation, apoptosis, or autophagy. These small noncoding molecules regulate post-transcriptional expression of targets genes via degradation of transcript or inhibition of protein synthesis. Aberrant expression and/or dysregulation of miRNAs have been characterized during tumor development and progression, thus, they are potential molecular targets for cancer prevention. The aim of this study was to investigate the effect of IP6 on the miRNAs expression profile in Caco-2 colon cancer cells. 84 miRNAs were analyzed in Caco-2 cells treated with 2.5 mM and 5 mM IP6 by the use of PCR (Polymerase Chain Reaction) array. The effect of 5 mM IP6 on selected potential miR-155 targets was determined by real-time (RT)-qPCR and ELISA (quantitative Polymerase Chain Reaction and Enzyme-Linked Immunosorbent Assay )method. The results indicated alteration in the specific 10 miRNA expression in human colon cancer cells following their treatment with 5 mM IP6. It down-regulated 8 miRNAs (miR-155, miR-210, miR-144, miR-194, miR-26b, miR-126, miR-302c, and miR-29a) and up-regulated 2 miRNAs (miR-223 and miR-196b). In silico analysis revealed that FOXO3a, HIF-1α, and ELK3 mRNAs are those of predicted targets of miR-155. IP6 at the concentration of 5 mM markedly induced FOXO3a and HIF-1a genes’ expression at both mRNA and protein level and decreased the amount of ELK3 mRNA as well as protein concentration in comparison to the control. In conclusion, the present study indicates that one of the mechanisms of antitumor potential of IP6 is down-regulation of the miR-155 expression in human colon cancer cells. Moreover, the expression of genes that are targeted by miRNA are also modulated by IP6.
Highlights
Chemoprevention is the use of natural, synthetic, or biologic chemical agents to suppress or to reverse the initial phase of carcinogenesis or to prevent carcinogenic progression to invasive cancer.Various epidemiological and preclinical studies have convincingly argued the role of some dietary agents, such as isoflavones, catechins, lycopene, or isothiocyanates, to be involved in preventing the occurrence of both solid and hematologic malignancies as well as their treatment [1,2].Inositol hexaphosphate (InsP6, IP6) is a natural fiber-associated dietary component mainly found in cereals, legumes, nuts, oil seeds, and wheat bran
We found that IP6 can exert its biological activity via influence on the expression of some microRNAs which post-transcriptionally control the expression of related genes and affect corresponding cellular processes
For the last few years, we have directed our attention to colorectal cancer (CRC), which is recognized as one of the most common malignant tumors of cancer-related deaths worldwide [33]
Summary
Chemoprevention is the use of natural, synthetic, or biologic chemical agents to suppress or to reverse the initial phase of carcinogenesis or to prevent carcinogenic progression to invasive cancer. Inositol hexaphosphate (InsP6, IP6) is a natural fiber-associated dietary component mainly found in cereals, legumes, nuts, oil seeds, and wheat bran. It is a derivative of myo-inositol, of which. IP6 has been shown to exert antioxidant, anti-inflammatory, and anti-aging effects in many biological systems. It participates in various vital cell functions such as signal transduction, RNA export, DNA repair, energy transduction, and ATP (Adenosine 50 -triphosphate) regeneration [5]
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