短链脂肪酸丁酸钠能增加人结直肠癌 HCT-116 细胞系中 miR-21、miR-143 和 miR-145 的表达

Parastoo Mohammadi, Flora Forouzesh, Fatemeh Kouhkan
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引用次数: 0

摘要

背景:丁酸钠(NaBu)是一种短链脂肪酸,是组蛋白去乙酰化酶抑制剂之一,可改变遗传和表观遗传表达。本研究旨在阐明 NaBu 对人类结直肠癌 HCT-116 细胞系中 miR-21、miR-143 和 miR-145 表达的影响。研究方法本研究在伊朗德黑兰伊斯兰阿扎德大学德黑兰医学科学院进行。在 24、48 和 72 小时内用不同浓度的 NaBu(6.25 mM 至 200 mM)处理 HCT-116 细胞系。采用 Real-Time-PCR 定量分析 miR-21、miR-143 和 miR-145 的基因表达。结果通过 MTT 试验评估了 IC50 值。在培养 24、48 和 72 小时后,HCT-116 的 IC50 值分别为 50 mM、12.5 mM 和 6.25 mM。Real-Time-PCR 结果显示,培养 24 小时后,50 mM NaBu 导致 miR-21、miR-143 和 miR-145 的表达显著上调(P<0.05)。培养 48 小时后,12.5 mM NaBu 会导致 miR-21、miR-143 和 miR-145 的表达明显上调(P<0.05)。用 6.25 mM NaBu 培养 72 小时后,与未处理的细胞相比,miR-21、miR-143 和 miR-145 的表达明显上调(P<0.05)。结论miR-21、miR-143 和 miR-145 表达的上调是由转录调控介导的,该 miR 启动子的激活受组蛋白乙酰化的调节。使用 NaBu 可能是改进基于 HDACi 药物的结肠癌疗法的一种有前途的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Short Chain Fatty Acid Sodium Butyrate Increases miR-21, miR-143 and miR-145 Expression in Human Colorectal Cancer HCT-116 Cell Line
Background: Sodium butyrate (NaBu) is a short-chain fatty acid; it is one of the histone deacetylase inhibitors, which can alter both genetic and epigenetic expressions. The present study aimed to elucidate the effect of NaBu on the expression of miR-21, miR-143, and miR-145 in human colorectal cancer HCT-116 cell lines. Methods: This study was done in Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. HCT-116 cell line was treated with diverse concentrations of NaBu (6.25 mM to 200 mM) at 24, 48, and 72 h. MTT assay was used for assessing the cytotoxicity. Quantitative Real-Time-PCR was performed to investigate the gene expression of miR-21, miR-143, and miR-145. Results: IC50 values were evaluated by MTT assay. IC50 for HCT-116 was 50 mM, 12.5 mM, and 6.25 mM for 24, 48, and 72 h of incubation, respectively. According to the Real-Time-PCR results, 50 mM NaBu after 24 h caused a significant up-regulation in the expression of the miR-21, miR-143, and miR-145 (P<0.05). In 48 h, incubation, 12.5 mM NaBu caused a significant up-regulation in the expression of the miR-21, miR-143, and miR-145 (P<0.05). In treated cells with 6.25 mM NaBu after 72 h of incubation caused a significant up-regulation in the expression of the miR-21, miR-143, and miR-145 compared with untreated cells (P<0.05). Conclusion: The upregulation of miR-21, miR-143, and miR-145 expression are mediated by transcriptional regulation and the activation of this miR promoter is modulated by histone acetylation. The employment of NaBu may represent a promising approach for improving HDACi drug-based therapies for colon cancers.
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