Regulation of MicroRNA-155 and Its Related Genes Expression by Inositol Hexaphosphate in Colon Cancer Cells

摘要

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 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 ( , , , , , , , and ) and up-regulated 2 miRNAs ( and ). In silico analysis revealed that , , and mRNAs are those of predicted targets of . IP6 at the concentration of 5 mM markedly induced and genes’ expression at both mRNA and protein level and decreased the amount of 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 expression in human colon cancer cells. Moreover, the expression of genes that are targeted by miRNA are also modulated by IP6.