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乳腺癌中频繁出现的微小RNA(miRNA)融合基因事件。

Frequent miRNA-convergent fusion gene events in breast cancer.

作者信息

Persson Helena, Søkilde Rolf, Häkkinen Jari, Pirona Anna Chiara, Vallon-Christersson Johan, Kvist Anders, Mertens Fredrik, Borg Åke, Mitelman Felix, Höglund Mattias, Rovira Carlos

机构信息

Department of Clinical Sciences Lund, Oncology and Pathology, Lund University Cancer Center, Lund University, SE-223 63, Lund, Sweden.

German Cancer Research Center, Division of Functional Genome Analysis, Heidelberg, Germany.

出版信息

Nat Commun. 2017 Oct 5;8(1):788. doi: 10.1038/s41467-017-01176-1.

Abstract

Studies of fusion genes have mainly focused on the formation of fusions that result in the production of hybrid proteins or, alternatively, on promoter-switching events that put a gene under the control of aberrant signals. However, gene fusions may also disrupt the transcriptional control of genes that are encoded in introns downstream of the breakpoint. By ignoring structural constraints of the transcribed fusions, we highlight the importance of a largely unexplored function of fusion genes. Here, we show, using breast cancer as an example, that miRNA host genes are specifically enriched in fusion genes and that many different, low-frequency, 5' partners may deregulate the same miRNA irrespective of the coding potential of the fusion transcript. These results indicate that the concept of recurrence, defined by the rate of functionally important aberrations, needs to be revised to encompass convergent fusions that affect a miRNA independently of transcript structure and protein-coding potential.Fusion gene research traditionally focuses on fusions that result in hybrid proteins or promoter switching events. Here, the authors demonstrate enrichment of fusions in miRNA host genes in breast cancer, highlighting that disparate fusions could have convergent impact on miRNA.

摘要

融合基因的研究主要集中在导致杂交蛋白产生的融合形成上,或者集中在使基因受异常信号控制的启动子切换事件上。然而,基因融合也可能破坏断点下游内含子中编码的基因的转录控制。通过忽略转录融合的结构限制,我们强调了融合基因一个很大程度上未被探索的功能的重要性。在这里,我们以乳腺癌为例表明,miRNA宿主基因在融合基因中特别富集,并且许多不同的低频5'伙伴可能会使同一miRNA失调,而与融合转录本的编码潜力无关。这些结果表明,由功能重要的畸变率定义的复发概念需要修订,以涵盖独立于转录本结构和蛋白质编码潜力而影响miRNA的趋同融合。融合基因研究传统上侧重于导致杂交蛋白或启动子切换事件的融合。在这里,作者证明了乳腺癌中miRNA宿主基因中融合的富集,强调不同的融合可能对miRNA产生趋同影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7680/5629207/168bf3dac272/41467_2017_1176_Fig1_HTML.jpg

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