Circular and Fusion RNAs in Medulloblastoma Development.
Circular and Fusion RNAs in Medulloblastoma Development.
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DOI：
10.3390/cancers14133134
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发表时间：
2022-06-26
期刊：
影响因子：
5.2
通讯作者：
Zaphiropoulos, Peter G.
中科院分区：
文献类型：
--
作者：
Azatyan, Ani;Zaphiropoulos, Peter G.
已知环状RNA的表达在癌症中失调。这里提供了髓母细胞瘤与小脑相比最全面的一组差异表达的RNA环。此外，融合RNA也在癌性和正常小脑组织中被鉴定。在髓母细胞瘤中检测到的一些融合是由连接不同基因的基因组重排产生的。然而，在正常小脑中也检测到融合RNA。事实上，在髓母细胞瘤中也发现了相同的融合RNA。这一观察结果强调了融合转录物的形成可能不限于染色体事件，但也可能是由在RNA水平上起作用的机制引起的。这些包括相邻基因的通读转录和来自不同基因的前mRNA的分子间剪接。重要的是，这些RNA“重组”事件不仅发生在正常组织中，而且发生在癌组织中。背景小脑癌髓母细胞瘤是最常见的儿童脑肿瘤。方法.使用流水线对81例髓母细胞瘤生物标本进行RNA测序，以检测环状和融合RNA。通过PCR和桑格测序进行验证。结果在SHH、WNT、第3组和第4组髓母细胞瘤亚型中，分别发现27、56、28和11个RNA环独特地上调，而149、7、20和15个独特地下调。此外，线性和环状融合RNA含有不同的基因在典型的剪接位点连接的外显子也被确定。这些通常表达少于环状RNA，然而线性和环状融合体的表达是相当的。重要的是，髓母细胞瘤中融合蛋白的表达也与小脑相当。结论.肿瘤中大量的融合可以通过与正常组织中产生融合的机制相似的机制产生。一些融合可以通过两个相邻基因的通读转录来合理化。然而，对于其他融合，例如，来自下游基因的外显子与来自上游基因的外显子5′至3′连接的线性融合，更复杂的剪接机制，例如，反式剪接，必须假设。
Expression of circular RNAs is known to be deregulated in cancer. Here the most comprehensive set of differentially expressed RNA circles in medulloblastoma compared to cerebellum is provided. Additionally, fusion RNAs are also identified in both cancerous and normal cerebellar tissue. Some of the fusions detected in medulloblastoma are generated by genomic rearrangements that link different genes. However, fusion RNAs are also detected in normal cerebellum. In fact, there are cases where the same fusion RNA is also found in medulloblastoma. This observation underscores that the formation of fusion transcripts may not be limited to chromosomal events but could also result from mechanisms that act at the RNA level. These include read-through transcription of neighboring genes and intermolecular splicing of pre-mRNAs from different genes Importantly, these RNA “recombination” events occur not only in normal but also in cancerous tissue. Background. The cerebellar cancer medulloblastoma is the most common childhood cancer in the brain. Methods. RNA sequencing of 81 human biospecimens of medulloblastoma using pipelines to detect circular and fusion RNAs. Validation via PCR and Sanger sequencing. Results. 27, 56, 28 and 11 RNA circles were found to be uniquely up-regulated, while 149, 7, 20 and 15 uniquely down-regulated in the SHH, WNT, Group 3, and Group 4 medulloblastoma subtypes, respectively. Moreover, linear and circular fusion RNAs containing exons from distinct genes joined at canonical splice sites were also identified. These were generally expressed less than the circular RNAs, however the expression of both the linear and the circular fusions was comparable. Importantly, the expression of the fusions in medulloblastoma was also comparable to that of cerebellum. Conclusions. A significant number of fusions in tumor may be generated by mechanisms similar to the ones generating fusions in normal tissue. Some fusions could be rationalized by read-through transcription of two neighboring genes. However, for other fusions, e.g., a linear fusion with an exon from a downstream gene joined 5′ to 3′ with an exon from an upstream gene, more complicated splicing mechanisms, e.g., trans-splicing, have to be postulated.
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影响因子：
14.9
作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.2
作者：
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髓母细胞瘤中失调的环状 RNA 通过宿主基因调节肿瘤细胞的增殖和生长。
影响因子：
4
作者：
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