Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with functional significance in prostate cancer.
Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with functional significance in prostate cancer.
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DOI：
10.1002/jev2.12210
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发表时间：
2022-05
影响因子：
16
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中科院分区：
文献类型：
--
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长链非编码（lnc）RNA在调节基因表达的同时，也是新抗原的一个意外来源。尽管它们备受关注，但它们能否转移并控制邻近细胞尚不清楚。细胞外囊泡（EVs）为核酸提供了一个保护环境，通过控制免疫反应具有促肿瘤和抗肿瘤的功能。与细胞外非囊泡RNA不同，很少有研究涉及人体体液中细胞外囊泡的全部RNA含量，并将其与来源组织进行比较。在此，我们对6例福尔马林固定石蜡包埋（FFPE）前列腺癌（PCa）肿瘤组织及其配对的尿液细胞外囊泡（uEVs）进行了全RNA测序，首次对同一患者进行了全转录组比较。尿液细胞外囊泡包含简化的转录组，具有无内含子的细胞质转录本以及富集的lnc/circular（circ）RNA，这在一个独立的20例患者尿液队列中非常常见。我们对三种前列腺癌细胞系进行的细胞和细胞外囊泡全转录组比较，确定了一组重叠的14种尿液细胞外囊泡circRNA，其特征是对体外前列腺细胞增殖至关重要，以及28种尿液细胞外囊泡lncRNA，它们属于癌症相关lncRNA普查（CLC2）。此外，我们发现了15种尿液细胞外囊泡lncRNA，预计可编码768种高亲和力新抗原，其中三种编码的开放阅读框（ORF）通过质谱法产生了可检测的未修饰肽。我们对尿液和体外细胞外囊泡中lnc/circRNA的双重分析，为未来涉及前列腺癌的尿液细胞外囊泡lnc/circRNA表型特征研究提供了重要资源。
Long noncoding (lnc)RNAs modulate gene expression alongside presenting unexpected source of neoantigens. Despite their immense interest, their ability to be transferred and control adjacent cells is unknown. Extracellular Vesicles (EVs) offer a protective environment for nucleic acids, with pro and antitumourigenic functions by controlling the immune response. In contrast to extracellular nonvesicular RNA, few studies have addressed the full RNA content within human fluids’ EVs and have compared them with their tissue of origin. Here, we performed Total RNA‐Sequencing on six Formalin‐Fixed‐Paraffin‐Embedded (FFPE) prostate cancer (PCa) tumour tissues and their paired urinary (u)EVs to provide the first whole transcriptome comparison from the same patients. UEVs contain simplified transcriptome with intron‐free cytoplasmic transcripts and enriched lnc/circular (circ)RNAs, strikingly common to an independent 20 patients’ urinary cohort. Our full cellular and EVs transcriptome comparison within three PCa cell lines identified a set of overlapping 14 uEV‐circRNAs characterized as essential for prostate cell proliferation in vitro and 28 uEV‐lncRNAs belonging to the cancer‐related lncRNA census (CLC2). In addition, we found 15 uEV‐lncRNAs, predicted to encode 768 high‐affinity neoantigens, and for which three of the encoded‐ORF produced detectable unmodified peptides by mass spectrometry. Our dual analysis of EVs‐lnc/circRNAs both in urines’ and in vitro’s EVs provides a fundamental resource for future uEV‐lnc/circRNAs phenotypic characterization involved in PCa.
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影响因子：
4.6
作者：
Bachmayr-Heyda A;Reiner AT;Auer K;Sukhbaatar N;Aust S;Bachleitner-Hofmann T;Mesteri I;Grunt TW;Zeillinger R;Pils D
通讯作者：
Pils D
影响因子：
4.6
作者：
Everaert, Celine;Helsmoortel, Hetty;Vandesompele, Jo
通讯作者：
Vandesompele, Jo
影响因子：
56.9
作者：
Chen, Jin;Brunner, Andreas-David;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.
影响因子：
64.8
作者：
Hsieh, Andrew C.;Liu, Yi;Edlind, Merritt P.;Ingolia, Nicholas T.;Janes, Matthew R.;Sher, Annie;Shi, Evan Y.;Stumpf, Craig R.;Christensen, Carly;Bonham, Michael J.;Wang, Shunyou;Ren, Pingda;Martin, Michael;Jessen, Katti;Feldman, Morris E.;Weissman, Jonathan S.;Shokat, Kevan M.;Rommel, Christian;Ruggero, Davide
通讯作者：
Ruggero, Davide
影响因子：
51.1
作者：
Cuzick, Jack;Swanson, Gregory P.;Fisher, Gabrielle;Brothman, Arthur R.;Berney, Daniel M.;Reid, Julia E.;Mesher, David;Speights, V. O.;Stankiewicz, Elzbieta;Foster, Christopher S.;Moller, Henrik;Scardino, Peter;Warren, Jorja D.;Park, Jimmy;Younus, Adib;Flake, Dart D., II;Wagner, Susanne;Gutin, Alexander;Lanchbury, Jerry S.;Stone, Steven
通讯作者：
Stone, Steven