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FTO 通过上调 LINC01559 抑制 miR-1343-3p 表达从而赋予乳腺癌细胞对多西紫杉醇的耐药性。

FTO-mediated epigenetic upregulation of LINC01559 confers cell resistance to docetaxel in breast carcinoma by suppressing miR-1343-3p.

机构信息

Department of Thyroid and Breast Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

出版信息

Kaohsiung J Med Sci. 2023 Sep;39(9):873-882. doi: 10.1002/kjm2.12728. Epub 2023 Aug 16.

Abstract

This study was to explore the regulatory effect of long non-coding RNA LINC01559 on Docetaxel resistance in breast carcinoma (BCa) and its underlying mechanism. In the present study, we found that LINC01559 expression was elevated and LINC01559 overexpression facilitated docetaxel resistance in BCa cells. Moreover, it was revealed that the upregulation of LINC01559 in BCa cells was induced by FTO-mediated demethylation in an m6A-YTHDF2-dependent manner. Additionally, Dual-luciferase reporter assay confirmed the binding ability between LINC01559 and miR-1343-3p, and Pearson correlation analysis showed a negative correlation between them. Particularly, miR-1343-3p inhibition partly abolished the suppression on docetaxel resistance in BCa cells caused by LINC01559 knockdown. To sum up, FTO-mediated epigenetic upregulation of LINC01559 promoted cell resistance to Docetaxel in BCa by negatively regulating miR-1343-3p.

摘要

本研究旨在探索长链非编码 RNA LINC01559 对乳腺癌(BCa)多西他赛耐药的调节作用及其潜在机制。在本研究中,我们发现 LINC01559 的表达上调,并且 LINC01559 的过表达促进了 BCa 细胞对多西他赛的耐药性。此外,研究表明 FTO 介导的去甲基化以 m6A-YTHDF2 依赖的方式诱导了 BCa 细胞中 LINC01559 的上调。此外,双荧光素酶报告基因检测证实了 LINC01559 与 miR-1343-3p 之间的结合能力,并且 Pearson 相关性分析显示它们之间呈负相关。特别地,miR-1343-3p 的抑制部分消除了 LINC01559 敲低引起的 BCa 细胞多西他赛耐药性的抑制。总之,FTO 介导的 LINC01559 的表观遗传上调通过负调控 miR-1343-3p 促进了 BCa 细胞对多西他赛的耐药性。

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