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微小RNA-524-5p通过靶向作用抑制乳腺癌细胞的迁移、侵袭和上皮-间质转化进程

MiR-524-5p Suppresses Migration, Invasion, and EMT Progression in Breast Cancer Cells Through Targeting .

作者信息

Jin Taobo, Zhang Yun, Zhang Tianya

机构信息

Department of Thyroid and Breast Surgery, Zhuji People's Hospital, Zhuji City, China.

出版信息

Cancer Biother Radiopharm. 2020 Dec;35(10):789-801. doi: 10.1089/cbr.2019.3046. Epub 2020 Apr 16.

Abstract

The effects of miR-524-5p on breast cancer (BC) have not been investigated, though studies show that miR-524-5p has an anticancer function. Thus, this study investigated the effects of miR-524-5p on BC cells and its potential molecular mechanism. The expression of miR-524-5p from the collected BC samples was determined. Cell counting kit-8 (CCK-8) assay was performed to examine the effect of miR-524-5p on BC cells viability. The target for miR-524-5p was predicted by bioinformatics and further verified by luciferase assay. Wound healing assay and transwell assay were performed to determine cell migration and invasion of BC cells. The expressions of Follistatin-like 1 () and related proteins in epithelial-mesenchymal transition (EMT) were detected by Western blotting and quantitative real-time polymerase chain reaction. MiR-524-5p was low-expressed in BC samples, and upregulation of miR-524-5p suppressed BC cell viability, migration, and invasion. was predicted as a target for miR-524-5p. In addition, overexpressed effectively abolished the effect of miR-524-5p on inhibiting FSTL1 expression, and reversed the inhibitory effects of miR-524-5p on the migration, invasion of BC cells as well as the effect of miR-524-5p on regulating the expressions of matrix metalloproteinase 2 (), matrix metalloproteinase 9 (), E-cadherin, and N-cadherin. Our findings suggest that miR-524-5p targeting adversely affects the progression of migration, invasion, and EMT of BC cells, thus, miR-524-5p is possibly a target for BC treatment.

摘要

尽管研究表明miR-524-5p具有抗癌功能,但尚未对其在乳腺癌(BC)中的作用进行研究。因此,本研究探讨了miR-524-5p对BC细胞的影响及其潜在的分子机制。测定了收集的BC样本中miR-524-5p的表达。采用细胞计数试剂盒-8(CCK-8)法检测miR-524-5p对BC细胞活力的影响。通过生物信息学预测miR-524-5p的靶标,并通过荧光素酶测定进一步验证。进行伤口愈合试验和Transwell试验以确定BC细胞的迁移和侵袭能力。通过蛋白质免疫印迹法和定量实时聚合酶链反应检测上皮-间质转化(EMT)中卵泡抑素样蛋白1(FSTL1)及相关蛋白的表达。miR-524-5p在BC样本中低表达,miR-524-5p的上调抑制了BC细胞的活力、迁移和侵袭。FSTL1被预测为miR-524-5p的靶标。此外,FSTL1的过表达有效消除了miR-524-5p对FSTL1表达的抑制作用,并逆转了miR-524-5p对BC细胞迁移、侵袭的抑制作用以及miR-524-5p对基质金属蛋白酶2(MMP2)、基质金属蛋白酶9(MMP9)、E-钙黏蛋白和N-钙黏蛋白表达的调节作用。我们的研究结果表明,miR-524-5p靶向FSTL1对BC细胞的迁移、侵袭和EMT进程产生不利影响,因此,miR-524-5p可能是BC治疗的一个靶点。

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