Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
Omiya City Clinic, Saitama, 330-8669, Japan.
J Hum Genet. 2021 Feb;66(2):181-191. doi: 10.1038/s10038-020-00826-5. Epub 2020 Sep 3.
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.
环状 RNA(circRNAs)是通过一种称为反向剪接的过程从前体 mRNA 产生的单链、共价闭合的 RNA 分子。尽管 circRNAs 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。与正常胰腺组织相比,我们在 PDAC 组织中鉴定出了超过 40000 个以前未知的 circRNAs,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 circRNA 来源于染色体 12 上的两个非编码 RNA 位点。新型 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。虽然推测了 circPDAC RNA 的生物学功能,如从 circPDAC RNA 产生肽,但在其他 PDAC 组织和 PDAC 患者的血清中都检测到了其异常表达。这些结果表明,有必要进行全面的研究来揭示 circRNAs 的表达状态,并且这里鉴定的 circPDAC RNA 可能作为包括 PDAC 在内的癌症的新型生物标志物。