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顺铂耐药 MCF-7 细胞的转录组变化。

Transcriptomic Changes in Cisplatin-Resistant MCF-7 Cells.

机构信息

Laboratorio de Epigenetica, Instituto Nacional de Medicina Genomica (INMEGEN), Ciudad de Mexico 14610, Mexico.

Posgrado en Ciencias Biomédicas, Universidad Nacional Autónoma de Mexico (UNAM), Ciudad de Mexico 04510, Mexico.

出版信息

Int J Mol Sci. 2024 Mar 29;25(7):3820. doi: 10.3390/ijms25073820.

Abstract

Breast cancer is a leading cause of cancer-related deaths among women. Cisplatin is used for treatment, but the development of resistance in cancer cells is a significant concern. This study aimed to investigate changes in the transcriptomes of cisplatin-resistant MCF7 cells. We conducted RNA sequencing of cisplatin-resistant MCF7 cells, followed by differential expression analysis and bioinformatic investigations to identify changes in gene expression and modified signal transduction pathways. We examined the size and quantity of extracellular vesicles. A total of 724 genes exhibited differential expression, predominantly consisting of protein-coding RNAs. Notably, two long non-coding RNAs (lncRNAs), NEAT1 and MALAT, were found to be dysregulated. Bioinformatic analysis unveiled dysregulation in processes related to DNA synthesis and repair, cell cycle regulation, immune response, and cellular communication. Additionally, modifications were observed in events associated with extracellular vesicles. Conditioned media from resistant cells conferred resistance to wild-type cells in vitro. Furthermore, there was an increase in the number of vesicles in cisplatin-resistant cells. Cisplatin-resistant MCF7 cells displayed differential RNA expression, including the dysregulation of NEAT1 and MALAT long non-coding RNAs. Key processes related to DNA and extracellular vesicles were found to be altered. The increased number of extracellular vesicles in resistant cells may contribute to acquired resistance in wild-type cells.

摘要

乳腺癌是导致女性癌症相关死亡的主要原因之一。顺铂被用于治疗,但癌细胞产生耐药性是一个重大问题。本研究旨在研究顺铂耐药 MCF7 细胞的转录组变化。我们对顺铂耐药 MCF7 细胞进行了 RNA 测序,随后进行了差异表达分析和生物信息学研究,以鉴定基因表达的变化和修饰的信号转导途径。我们检查了细胞外囊泡的大小和数量。共有 724 个基因表现出差异表达,主要由蛋白质编码 RNA 组成。值得注意的是,两个长非编码 RNA(lncRNA),NEAT1 和 MALAT,被发现失调。生物信息学分析揭示了与 DNA 合成和修复、细胞周期调控、免疫反应和细胞通讯相关过程的失调。此外,还观察到与细胞外囊泡相关事件的修饰。耐药细胞的条件培养基在体外赋予野生型细胞耐药性。此外,耐药细胞中的囊泡数量增加。顺铂耐药 MCF7 细胞显示出差异的 RNA 表达,包括 NEAT1 和 MALAT 长非编码 RNA 的失调。与 DNA 和细胞外囊泡相关的关键过程被发现发生了改变。耐药细胞中外泌体数量的增加可能导致野生型细胞获得耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bc/11011657/b607d008e12d/ijms-25-03820-g001.jpg

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