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The Effect of Methylselenocysteine and Sodium Selenite Treatment on microRNA Expression in Liver Cancer Cell Lines
Pathology & Oncology Research ( IF 2.3 ) Pub Date : 2020-07-12 , DOI: 10.1007/s12253-020-00870-8
Gábor Lendvai 1 , Tímea Szekerczés 1 , Endre Kontsek 1 , Arun Selvam 2 , Attila Szakos 2 , Zsuzsa Schaff 1 , Mikael Björnstedt 2 , András Kiss 1
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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, IC50 values were determined by performing SRB proliferation assays. The results revealed much lower IC50 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 IC50. 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.



中文翻译:

甲基硒代半胱氨酸和亚硒酸钠处理对肝癌细胞系中 microRNA 表达的影响

硒化合物(包括亚硒酸钠和硒-甲基硒代半胱氨酸(MSC))的独特之处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,硒治疗可能会影响 microRNA (miRNA) 的表达,因为在安慰剂对照的硒补充剂研究中,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 miRNA,并在亚硒酸盐或 MSC 治疗后使用单独的 TaqMan MicroRNA 检测在肝细胞癌(HLE 和 HLF)和胆管癌细胞系(TFK-1 和 HuH-28)中测量它们的表达。为了建立耐受浓度,通过进行SRB增殖测定来确定IC 50值。结果显示,与 MSC(79.5 至 322.6 μM)相比,亚硒酸盐的IC 50值(从 2.7 至 11.3 μM)低得多。这些处理导致了细胞系依赖性 miRNA 表达模式,所有 miRNA 都表现出倍数变化差异;然而,与低于​​ IC 50 的未处理细胞相比,处理细胞中只有少数变化存在统计学差异。即,MSC处理后HLF中的miR-199a、TFK-1中的miR-143、HLF中的miR-210和亚硒酸盐处理后HLF中的TFK-1、miR-22、-24、-122、-143。倍数变化差异表明,miR-122 与两种硒化合物、miR-199a 与 MSC 以及 miR-22 与亚硒酸盐均受到影响。显示出最小改变的 miRNA 包括 miR-125b 和 miR-194。总之,我们的结果显示细胞系中 miRNA 表达发生适度改变(MSC 处理后改变较小),其中 miR-122、-199a 受影响最大,miR-125b、-194 是硒处理后改变最小的 miRNA。

更新日期:2020-07-12
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