Distinct Small RNA Signatures in Extracellular Vesicles Derived from Breast Cancer Cell Lines.

Distinct Small RNA Signatures in Extracellular Vesicles Derived from Breast Cancer Cell Lines.
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DOI:
10.1371/journal.pone.0161824
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Seternes OM
Seternes OM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fiskaa T;Knutsen E;Nikolaisen MA;Jørgensen TE;Johansen SD;Perander M;Seternes OM

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乳腺癌是一种异质性疾病,不同亚型的乳腺癌表现出不同的细胞形态、基因表达、代谢、运动性、增殖和转移潜力。了解导致这种异质性的分子特征对于正确诊断和更好的治疗策略非常重要。细胞外囊泡(EV)及其相关分子作为细胞间通讯的参与者、为转移性侵袭预处理特定器官的能力以及作为循环癌症生物标志物的潜在作用而受到广泛关注。EV从细胞中释放出来,含有蛋白质、DNA和长RNA和小RNA。在这里,我们通过高通量小RNA测序表明,来自9种不同乳腺癌细胞系的EV在小RNA含量方面具有共同的特征,这些特征与其起源细胞不同。最引人注目的是,来自核28 S rRNA的高度丰富的小RNA分子在EV中大量富集。EV中的miRNA谱与细胞miRNA表达模式相关,但包括miR-21在内的少数例外。这种癌症相关的miRNA保留在乳腺癌细胞系中。最后,我们报告说,与来自其他癌细胞系的EV相比,来自乳腺癌细胞系的EV基于其小RNA特征聚集在一起。总之,我们的数据表明,乳腺癌细胞系在其释放的EV中表现出特定的小RNA特征。这为进一步评估EV作为乳腺癌生物标志物开辟了道路。
Breast cancer is a heterogeneous disease, and different subtypes of breast cancer show distinct cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. Understanding the molecular features responsible for this heterogeneity is important for correct diagnosis and better treatment strategies. Extracellular vesicles (EVs) and their associated molecules have gained much attention as players in intercellular communication, ability to precondition specific organs for metastatic invasion, and for their potential role as circulating cancer biomarkers. EVs are released from the cells and contain proteins, DNA, and long and small RNA species. Here we show by high-throughput small RNA-sequencing that EVs from nine different breast cancer cell lines share common characteristics in terms of small RNA content that are distinct from their originating cells. Most strikingly, a highly abundant small RNA molecule derived from the nuclear 28S rRNA is vastly enriched in EVs. The miRNA profiles in EVs correlate with the cellular miRNA expression pattern, but with a few exceptions that includes miR-21. This cancer-associated miRNA is retained in breast cancer cell lines. Finally, we report that EVs from breast cancer cell lines cluster together based on their small RNA signature when compared to EVs derived from other cancer cell lines. Altogether, our data demonstrate that breast cancer cell lines manifest a specific small RNA signature in their released EVs. This opens up for further evaluation of EVs as breast cancer biomarkers.
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