肌醇六磷酸对结肠癌细胞中 microRNA-155 及其相关基因表达的调控。
Regulation of MicroRNA-155 and Its Related Genes Expression by Inositol Hexaphosphate in Colon Cancer Cells.
机构信息
Department of Biochemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jedności 8, 41-200 Sosnowiec, Poland.
出版信息
Molecules. 2019 Nov 16;24(22):4153. doi: 10.3390/molecules24224153.
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.
肌醇六磷酸（IP6），一种天然的膳食成分，已被发现作为一种抗肿瘤剂，通过刺激细胞凋亡和抑制癌细胞增殖、迁移和转移来发挥作用，其在包括结肠癌在内的多种癌症中都有应用。然而，其作用的分子机制尚不清楚。近年来，microRNAs（miRNAs）已被报道在广泛的生物学过程中发挥重要作用，如细胞生长、增殖、凋亡或自噬。这些小的非编码分子通过降解转录物或抑制蛋白质合成来调节靶基因的转录后表达。miRNAs 的异常表达和/或失调已在肿瘤发生和发展过程中得到描述，因此，它们是癌症预防的潜在分子靶点。本研究旨在探讨 IP6 对 Caco-2 结肠癌细胞中 miRNAs 表达谱的影响。使用 PCR（聚合酶链反应）阵列分析了用 2.5mM 和 5mM IP6 处理的 Caco-2 细胞中的 84 种 miRNAs。通过实时（RT）-qPCR 和 ELISA（定量聚合酶链反应和酶联免疫吸附测定）方法确定 5mM IP6 对选定的潜在靶点的影响。结果表明，用 5mM IP6 处理人结肠癌细胞后，特定的 10 种 miRNA 的表达发生改变。它下调了 8 种 miRNA（、、、、、、和），上调了 2 种 miRNA（和）。计算机分析显示，、和 mRNAs 是 的预测靶标。在浓度为 5mM 时，IP6 明显诱导 和 基因在 mRNA 和蛋白质水平上的表达，并降低了 mRNA 的数量以及与对照组相比的蛋白质浓度。总之，本研究表明，IP6 抗肿瘤潜力的机制之一是下调人结肠癌细胞中 的表达。此外，miRNA 靶向的基因的表达也被 IP6 调节。
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