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乳腺癌和 DCIS 患者来源的外泌体中 miR-16、miR-30b 和 miR-93 的不同特征。

Different signatures of miR-16, miR-30b and miR-93 in exosomes from breast cancer and DCIS patients.

机构信息

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.

Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.

出版信息

Sci Rep. 2018 Aug 28;8(1):12974. doi: 10.1038/s41598-018-31108-y.

Abstract

Loading of microRNAs (miRNAs) into exosomes that are involved in cellular communication is a selective process. The current study investigates whether the enrichment of miRNAs in exosomes reflects the pathogenesis of breast cancer (BC) and ductal carcinoma in situ (DCIS). The levels of miRNAs were quantified in exosomes from plasma of 32 BC patients, 8 DCIS patients and 8 healthy women by TaqMan real-time PCR-based miRNA array cards containing 47 different miRNAs. Then, exosomal miR-16, miR-30b and miR-93 that displayed deregulation in the arrays were selected and analyzed in 111 BC patients, 42 DCIS patients and 39 healthy women by TaqMan real-time PCR. Identification of exosomes was performed by Western blot. The levels of exosomal miR-16 were higher in plasma of BC (p = 0.034) and DCIS (p = 0.047) patients than healthy women, and were associated with estrogen (p = 0.004) and progesterone (p = 0.008) receptor status. Particularly, in estrogen-positive patients miR-16 was significantly enriched in exosomes (p = 0.0001). Lower levels of exosomal miR-30b were associated with recurrence (p = 0.034). Exosomal miR-93 was upregulated in DCIS patients (p = 0.001). Our findings suggest that different signatures of miR-16, miR-30b and miR-93 in exosomes from BC and DCIS patients are associated with a particular biology of breast tumors.

摘要

将 microRNAs(miRNAs)加载到参与细胞通讯的外泌体中是一个选择性过程。本研究旨在探讨外泌体中 miRNAs 的富集是否反映了乳腺癌(BC)和导管原位癌(DCIS)的发病机制。通过包含 47 种不同 miRNAs 的 TaqMan 实时 PCR 基于 miRNA 阵列卡定量分析了 32 例 BC 患者、8 例 DCIS 患者和 8 例健康女性血浆中外泌体中的 miRNAs 水平。然后,通过 TaqMan 实时 PCR 分析了阵列中显示失调的外泌体 miR-16、miR-30b 和 miR-93,在 111 例 BC 患者、42 例 DCIS 患者和 39 例健康女性中进行了分析。Western blot 用于鉴定外泌体。BC(p=0.034)和 DCIS(p=0.047)患者血浆中外泌体 miR-16 水平高于健康女性,与雌激素(p=0.004)和孕激素(p=0.008)受体状态相关。特别是在雌激素阳性患者中外泌体 miR-16 明显富集(p=0.0001)。外泌体 miR-30b 水平较低与复发相关(p=0.034)。DCIS 患者中外泌体 miR-93 上调(p=0.001)。我们的研究结果表明,BC 和 DCIS 患者外泌体中不同的 miR-16、miR-30b 和 miR-93 特征与特定的乳腺肿瘤生物学相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f3e/6113263/dbebd108ad8a/41598_2018_31108_Fig1_HTML.jpg

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