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甲硫氨酸硒和亚硒酸钠处理对肝癌细胞系中 microRNA 表达的影响。

The Effect of Methylselenocysteine and Sodium Selenite Treatment on microRNA Expression in Liver Cancer Cell Lines.

机构信息

2nd Department of Pathology, Semmelweis University, Ulloi 93, Budapest, H-1091, Hungary.

Division of Pathology, F46, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-14186, Stockholm, Sweden.

出版信息

Pathol Oncol Res. 2020 Oct;26(4):2669-2681. doi: 10.1007/s12253-020-00870-8. Epub 2020 Jul 12.

Abstract

The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells, providing a great potential for treating cancer cells being highly resistant to cytostatic drugs. However, selenium treatment may affect microRNA (miRNA) expression as the pattern of circulating miRNAs changed in a placebo-controlled selenium supplement study. This necessitates exploring possible changes in the expression profiles of miRNAs. For this, miRNAs being critical for liver function were selected and their expression was measured in hepatocellular carcinoma (HLE and HLF) and cholangiocarcinoma cell lines (TFK-1 and HuH-28) using individual TaqMan MicroRNA Assays following selenite or MSC treatments. For establishing tolerable concentrations, IC values were determined by performing SRB proliferation assays. The results revealed much lower IC values for selenite (from 2.7 to 11.3 μM) compared to MSC (from 79.5 to 322.6 μM). The treatments resulted in cell line-dependent miRNA expression patterns, with all miRNAs found to show fold change differences; however, only a few of these changes were statistically different in treated cells compared to untreated cells below IC. Namely, miR-199a in HLF, miR-143 in TFK-1 upon MSC treatment, miR-210 in HLF and TFK-1, miR-22, -24, -122, -143 in HLF upon selenite treatment. Fold change differences revealed that miR-122 with both selenium compounds, miR-199a with MSC and miR-22 with selenite were affected. The miRNAs showing minimal alterations included miR-125b and miR-194. In conclusion, our results revealed moderately altered miRNA expression in the cell lines (less alterations following MSC treatment), being miR-122, -199a the most affected and miR-125b, -194 the least altered miRNAs upon selenium treatment.

摘要

硒化合物的独特性质,包括亚硒酸钠和 Se-甲基硒代半胱氨酸 (MSC),在于它们对肿瘤细胞具有细胞毒性作用,为治疗对细胞抑制剂高度耐药的癌细胞提供了巨大的潜力。然而,硒处理可能会影响 microRNA(miRNA)的表达,因为在一项安慰剂对照的硒补充研究中,循环 miRNA 的模式发生了变化。这就需要探索 miRNA 表达谱可能发生的变化。为此,选择了对肝功能至关重要的 miRNAs,并在亚硒酸钠或 MSC 处理后使用单个 TaqMan MicroRNA 测定法测量肝癌 (HLE 和 HLF) 和胆管癌细胞系 (TFK-1 和 HuH-28) 中的表达。为了确定可耐受的浓度,通过进行 SRB 增殖测定法确定 IC 值。结果表明,与 MSC(从 79.5 到 322.6 μM)相比,亚硒酸钠的 IC 值低得多(从 2.7 到 11.3 μM)。处理导致细胞系依赖性 miRNA 表达模式,所有 miRNA 均显示出倍数变化差异;然而,只有少数这些变化在低于 IC 的未处理细胞与处理细胞之间存在统计学差异。即 MSC 处理后 HLF 中的 miR-199a、TFK-1 中的 miR-143、HLF 和 TFK-1 中的 miR-210、HLF 中的 miR-22、-24、-122、-143 中的 miR-122 处理后有亚硒酸钠。倍数变化差异表明,两种硒化合物均受 miR-122 影响,MSC 受 miR-199a 影响,而 selenite 受 miR-22 影响。受最小改变影响的 miRNA 包括 miR-125b 和 miR-194。总之,我们的结果表明细胞系中 miRNA 表达发生了适度改变(MSC 处理后改变较少),miR-122、-199a 受影响最大,miR-125b、-194 受影响最小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dd6/7471166/ff952e3ce925/12253_2020_870_Fig1_HTML.jpg

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