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硼酸治疗对乳腺癌干细胞中微小RNA - 127 - 5p及转移基因调控的评估

Evaluation of Boric Acid Treatment on microRNA-127-5p and Metastasis Genes Orchestration of Breast Cancer Stem Cells.

作者信息

Semerci Sevimli Tuğba, Ghorbani Aynaz, Gakhiyeva Fidan, Ebrahimi Aliakbar, Ghorbanpoor Hamed, Altuğ Burcugül, Ergen Fulya Buge, Ahmadova Zarifa, Soykan Merve Nur, Tufekcioglu Emre

机构信息

Cellular Therapy and Stem Cell Production, Application, and Research Center (ESTEM), Eskisehir Osmangazi University, Eskisehir, 26040, Turkey.

Department of Biomedical Engineering, Faculty of Engineering and Architecture, Eskisehir Osmangazi University, Eskisehir, 26040, Turkey.

出版信息

Biol Trace Elem Res. 2025 Mar;203(3):1465-1474. doi: 10.1007/s12011-024-04274-6. Epub 2024 Jul 4.

Abstract

Coregulation of microRNAs (miRNAs) and cancer stem cells (CSCs) is very important in carcinogenesis. miR-127-5p is known to be downregulated in breast cancer. In this study, we aimed to investigate how boric acid (BA), known for its previously unstudied anti-cancer properties, would affect the expression of miR127-5p and genes responsible for breast cancer stem cells (BC-SCs) metastasis. BC-SCs were isolated from human breast cancer cells (MCF-7) by immunomagnetic cell separation and characterized with flow cytometry and sphere formation. The viability of BC-SCs and the determination of its IC50 value in response to boric acid (BA) were assessed via the MTT assay. Boric acid exhibited dose- and time-dependent inhibition of cell viability in cells. The IC50 doses of boric acid in MCF-7 cells and BC-SCs were 45.69 mM and 41.27 mM, respectively. The impact of BA on the expression of metastatic genes and miR127-5p was elucidated through RT-qPCR analysis. While the expression of the COL1A1 (p < 0.05) and VIM (p < 0.01) was downregulated, the expression of the miR-127-5p, ZEB1 (p < 0.01), CDH1 (p < 0.05), ITGB1 (p < 0.05), ITGA5 (p < 0.05), LAMA5 (p < 0.01), and SNAIL (p < 0.05), was up-regulated in dose-treated BC-SCs (p < 0.001) to the RT-qPCR results. Our findings suggest that boric acid could induce miR-127-5p expression. However, it cannot be said that it improves the metastasis properties of breast cancer stem cells.

摘要

微小RNA(miRNA)与癌症干细胞(CSC)的共同调控在肿瘤发生过程中非常重要。已知miR-127-5p在乳腺癌中表达下调。在本研究中,我们旨在探究此前未被研究过的具有抗癌特性的硼酸(BA)如何影响miR-127-5p的表达以及负责乳腺癌干细胞(BC-SC)转移的基因。通过免疫磁珠细胞分选从人乳腺癌细胞(MCF-7)中分离出BC-SC,并通过流式细胞术和球形成实验对其进行表征。通过MTT实验评估BC-SC的活力及其对硼酸(BA)的IC50值。硼酸对细胞活力呈现出剂量和时间依赖性抑制作用。硼酸在MCF-7细胞和BC-SC中的IC50剂量分别为45.69 mM和41.27 mM。通过RT-qPCR分析阐明了BA对转移基因和miR-127-5p表达的影响。RT-qPCR结果显示,在经剂量处理的BC-SC中,COL1A1(p < 0.05)和波形蛋白(VIM,p < 0.01)的表达下调,而miR-127-5p、锌指蛋白E盒结合同源异形盒1(ZEB1,p < 0.01)、钙黏蛋白1(CDH1,p < 0.05)、整合素β1(ITGB1,p < 0.05)、整合素α5(ITGA5,p < 0.05)、层粘连蛋白α5(LAMA5,p < 0.01)和蜗牛蛋白(SNAIL,p < 0.05)的表达上调(p < 0.001)。我们的研究结果表明硼酸可诱导miR-127-5p表达。然而,不能说它改善了乳腺癌干细胞的转移特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e88c/11872770/ac3f346f9862/12011_2024_4274_Fig1_HTML.jpg

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