Aberrant expression of a novel circular RNA in pancreatic cancer

Aberrant expression of a novel circular RNA in pancreatic cancer
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DOI:
10.1038/s10038-020-00826-5
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发表时间:
2020-09-03
影响因子:
3.5
通讯作者:
Koike, Kazuhiko
Koike, Kazuhiko
中科院分区:
生物学3区
文献类型:
--
作者:
Seimiya, Takahiro;Otsuka, Motoyuki;Koike, Kazuhiko

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环状RNA(circRNA)是单链、共价闭合的RNA分子,其通过称为反向剪接的过程由前mRNA产生。尽管circRNA在特定条件下表达,但目前对其全面表达状态的了解仍然有限。在这里,我们使用环状RNA特异性RNA测序在人胰腺导管腺癌(PDAC)组织中进行了大规模的circRNA分析。我们鉴定了超过40,000种以前未知的circRNA,与正常胰腺组织相比,其中一些在PDAC组织中上调。我们确定了PDAC中上调的circRNA的全长序列,该序列来自12号染色体上的两个非编码RNA位点。新的circRNA,命名为circPDAC RNA,在正常人细胞中不表达,但在PDAC和其他癌细胞中表达。虽然没有检测到假定的生物学功能,例如从circPDAC RNA产生肽,但在其他PDAC组织和PDAC患者的血清中证实了其异常表达。这些结果表明,全面的研究是必要的,以揭示circRNA的表达状态,这里确定的circPDAC RNA可能作为一种新的生物标志物的癌症,包括PDAC。
Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are produced from pre-mRNAs through a process known as back-splicing. Although circRNAs are expressed under specific conditions, current understanding of their comprehensive expression status is still limited. Here, we performed a large-scale circRNA profiling analysis in human pancreatic ductal adenocarcinoma (PDAC) tissues, using circular RNA-specific RNA sequencing. We identified more than 40,000 previously unknown circRNAs, some of which were upregulated in PDAC tissues, compared with normal pancreatic tissues. We determined the full-length sequence of a circRNA upregulated in PDAC, which was derived from two noncoding RNA loci on chromosome 12. The novel circRNA, named circPDAC RNA, was not expressed in normal human cells, but was expressed in PDAC and other carcinoma cells. While postulated biological functions, such as peptide production from the circPDAC RNA, were not detected, its aberrant expression was confirmed in other PDAC tissues and in serum from a PDAC patient. These results demonstrate that comprehensive studies are necessary to reveal the expression status of circRNAs and that the circPDAC RNA identified here might serve as a novel biomarker for cancers, including PDAC.