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利用功能获得性筛选鉴定三阴性乳腺癌中参与紫杉醇耐药的微小RNA

Use of Gain-of-Function Screening to Identify miRNAs Involved in Paclitaxel Resistance in Triple-Negative Breast Cancer.

作者信息

Nemours Stéphane, Solé Carla, Goicoechea Ibai, Armesto María, Arestin María, Urruticoechea Ander, Rezola Marta, López Isabel Álvarez, Schaapveld Roel, Schultz Iman, Zhang Lei, Lawrie Charles H

机构信息

Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastian, Spain.

Department of Personalized Medicine, NASERTIC, Government of Navarra, 31011 Pamplona, Spain.

出版信息

Int J Mol Sci. 2024 Dec 20;25(24):13630. doi: 10.3390/ijms252413630.

DOI:10.3390/ijms252413630
PMID:39769392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11728027/
Abstract

Paclitaxel is a widely used chemotherapeutic agent for the treatment of breast cancer (BC), including as a front-line treatment for triple-negative breast cancer (TNBC) patients. However, resistance to paclitaxel remains one of the major causes of death associated with treatment failure. Multiple studies have demonstrated that miRNAs play a role in paclitaxel resistance and are associated with both disease progression and metastasis. In the present study, we used a miRNA-encoding lentiviral library as a gain-of-function screen for paclitaxel resistance in the MDA-MB-231 TNBC cell line. We identified that , , , and conferred a resistant phenotype to cells. The expression of also induced resistance to eribulin and vinorelbine, while and induced resistance to vinorelbine. We measured the levels of these miRNAs in breast cancer patients and observed higher levels of in treatment-refractory patients. Taken together, we suggest that and may be good candidates for miRNA inhibition to overcome resistance to chemotherapy.

摘要

紫杉醇是一种广泛用于治疗乳腺癌（BC）的化疗药物，包括作为三阴性乳腺癌（TNBC）患者的一线治疗药物。然而，对紫杉醇的耐药性仍然是与治疗失败相关的主要死亡原因之一。多项研究表明，微小RNA（miRNA）在紫杉醇耐药中起作用，并且与疾病进展和转移均相关。在本研究中，我们使用了一个编码miRNA的慢病毒文库，对MDA-MB-231 TNBC细胞系中的紫杉醇耐药性进行功能获得性筛选。我们鉴定出 、 、 、 和 赋予细胞耐药表型。 的表达还诱导了对艾日布林和长春瑞滨的耐药性，而 和 诱导了对长春瑞滨的耐药性。我们测量了乳腺癌患者中这些miRNA的水平，并观察到难治性患者中 的水平较高。综上所述，我们认为 和 可能是抑制miRNA以克服化疗耐药性的良好候选者。

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