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MUSASHI1 在乳腺癌上皮细胞中的表达增加是由于 miR-125b 的下调。

Increased expression of MUSASHI1 in epithelial breast cancer cells is due to down regulation of miR-125b.

机构信息

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar Jerib Ave., Azadi Square, Isfahan, P.O. Code 81746, Iran.

Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, P.O. Code 816513-1378, Iran.

出版信息

BMC Mol Cell Biol. 2021 Feb 4;22(1):10. doi: 10.1186/s12860-021-00348-8.

Abstract

BACKGROUND

Musashi1 (MSI1) is an oncogenic protein with a crucial role in the proliferation and characteristics of the epithelial cells in breast cancer. The change in expression of MSI1 has a role in solid tumor progression. There are different factors that regulate MSI1 expression in various cancer tissues including microRNAs which are considered as one of the most important of these factors. The aim of our study is identification of the molecular cause of maximal expression of MSI1 in epithelial breast cancer cell lines.

RESULTS

Among predicted microRNAs, miR-125b, miR-637 and miR-802 were able to significantly reduce the luciferase activity. In addition, the relative expression of these three miRNAs were measured in the cancerous cell lines that results showed a significant reduction in expression of all microRNAs. On the other hand, only the overexpression of miR-125b caused a change in the expression pattern of MSI1 in breast epithelial cancer cell lines. Accordingly, our results demonstrated that the exogenous expression of miR-125b decreased not only the MSI1 protein but also expression of epithelial markers in breast cancer cells.

CONCLUSIONS

The results of luciferase reporter assay showed that MSI1 is a direct target for miR-125b in epithelial breast cancer cells. Moreover, higher amount of MSI1 in those cell lines seems due to the reduced amount of miR-125b, which is responsible for epithelial features of those kinds of cancer cells. Therefore, the modulation of miR-125b may be a potential approach to help to combat against epithelial breast tumors.

摘要

背景

Musashi1(MSI1)是一种致癌蛋白,在乳腺癌上皮细胞的增殖和特征中起着关键作用。MSI1 的表达变化在实体瘤进展中起作用。有不同的因素调节各种癌症组织中的 MSI1 表达,包括 microRNAs,它们被认为是最重要的因素之一。我们研究的目的是确定 MSI1 在乳腺癌上皮细胞系中最大表达的分子原因。

结果

在预测的 microRNAs 中,miR-125b、miR-637 和 miR-802 能够显著降低荧光素酶活性。此外,还测量了这些 microRNAs 在癌细胞系中的相对表达水平,结果表明所有 microRNAs 的表达均显著降低。另一方面,只有 miR-125b 的过表达导致乳腺癌上皮细胞系中 MSI1 表达模式发生变化。因此,我们的结果表明,外源性表达 miR-125b 不仅降低了 MSI1 蛋白的表达,还降低了乳腺癌细胞中上皮标志物的表达。

结论

荧光素酶报告基因检测结果表明,MSI1 是乳腺癌上皮细胞中 miR-125b 的直接靶标。此外,这些细胞系中 MSI1 含量较高似乎是由于 miR-125b 含量减少所致,这是这些癌细胞上皮特征的原因。因此,miR-125b 的调节可能是对抗上皮性乳腺癌的一种潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dcc/7863248/555b2af76343/12860_2021_348_Fig1_HTML.jpg

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