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非小细胞肺癌中的组织和外泌体 miRNA 编辑。

Tissue and exosomal miRNA editing in Non-Small Cell Lung Cancer.

机构信息

Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH, USA.

Division of Pulmonary Diseases and Critical Care Medicine, Virginia Commonwealth University, Richmond, VA, USA.

出版信息

Sci Rep. 2018 Jul 5;8(1):10222. doi: 10.1038/s41598-018-28528-1.

DOI:10.1038/s41598-018-28528-1
PMID:29976955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6033928/
Abstract

RNA editing in microRNAs has been recently proposed as a novel biomarker in cancer. Here, we investigated RNA editing by leveraging small-RNA sequencing data from 87 NSCLC (Non-Small Cell Lung Cancer) samples paired with normal lung tissues from The Cancer Genome Atlas (TCGA) combined with 26 plasma-derived exosome samples from an independent cohort. Using both the editing levels and microRNA editing expression, we detected deregulated microRNA editing events between NSCLC tumor and normal tissues. Interestingly, and for the first time, we also detected editing sites in the microRNA cargo of circulating exosomes, providing the potential to non-invasively discriminate between normal and tumor samples. Of note, miR-411-5p edited in position 5 was significantly dysregulated in tissues as well as in exosomes of NSCLC patients, suggesting a potential targetome shift relevant to lung cancer biology.

摘要

RNA 编辑在 microRNAs 中最近被提出作为癌症的一种新的生物标志物。在这里,我们利用来自 87 个非小细胞肺癌 (NSCLC) 样本和来自癌症基因组图谱 (TCGA) 的配对正常肺组织的小 RNA 测序数据,以及来自独立队列的 26 个血浆衍生的外泌体样本,研究了 RNA 编辑。使用编辑水平和 microRNA 编辑表达,我们检测到 NSCLC 肿瘤和正常组织之间 microRNA 编辑事件的失调。有趣的是,也是第一次,我们还在循环外泌体的 microRNA 货物中检测到了编辑位点,为非侵入性区分正常和肿瘤样本提供了潜力。值得注意的是,在位置 5 编辑的 miR-411-5p 在组织和 NSCLC 患者的外泌体中均显著失调,提示与肺癌生物学相关的潜在靶标转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/7280367e59d8/41598_2018_28528_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/64cce1a365a3/41598_2018_28528_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/377e5e70fa0e/41598_2018_28528_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/1f3b0b3c5ce5/41598_2018_28528_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/7280367e59d8/41598_2018_28528_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/64cce1a365a3/41598_2018_28528_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/377e5e70fa0e/41598_2018_28528_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/1f3b0b3c5ce5/41598_2018_28528_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9635/6033928/7280367e59d8/41598_2018_28528_Fig4_HTML.jpg

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本文引用的文献

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Nat Commun. 2018 Jan 31;9(1):461. doi: 10.1038/s41467-018-02851-7.
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When MicroRNAs Meet RNA Editing in Cancer: A Nucleotide Change Can Make a Difference.当 microRNAs 遇见癌症中的 RNA 编辑:一个核苷酸的改变就能产生差异。
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The landscape of miRNA editing in animals and its impact on miRNA biogenesis and targeting.
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RNA Editing in Cancer Progression.癌症进展中的RNA编辑
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Identification of microRNA editing sites in clear cell renal cell carcinoma.鉴定肾透明细胞癌中的 microRNA 编辑位点。
Sci Rep. 2023 Sep 13;13(1):15117. doi: 10.1038/s41598-023-42302-y.
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Brain Topogr. 2024 Mar;37(2):243-264. doi: 10.1007/s10548-023-01004-4. Epub 2023 Sep 13.
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A-to-I edited miR-411-5p targets MET and promotes TKI response in NSCLC-resistant cells.A-to-I 编辑的 miR-411-5p 靶向 MET 并促进 NSCLC 耐药细胞对 TKI 的反应。
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