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Aberrant expression of a novel circular RNA in pancreatic cancer

Journal of Human Genetics volume 66, pages 181–191 (2021)Cite this article

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Abstract

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.

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Data availability

The authors declare that all the data supporting the findings of this study are presented within the article or the supplementary information files, and are available upon reasonable request to the corresponding author. The RNA sequencing data have been deposited in the Sequence Read Archive database (http://www.ncbi.nlm.nih.gov/sra) under the accession code PRJNA591376.

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Acknowledgements

This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (#19H03430, #18H05024, and #19J11829) (to MO, MO, and KS), by The Translational Research program; Strategic promotion for practical application of innovative medical technology, TR-SPRINT, from the Japan Agency for Medical Research and Development, AMED (to MO), by the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from AMED (to MO, #JP19cm0106602), and by the grants from Kobayashi Foundation for Cancer Research, All Japan Coffee Association, and Japan Foundation for Applied Enzymology (to MO).

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan

    Takahiro Seimiya, Motoyuki Otsuka, Takuma Iwata, Eri Tanaka, Kazuma Sekiba, Chikako Shibata & Kazuhiko Koike

  2. Omiya City Clinic, Saitama, 330-8669, Japan

    Masaru Moriyama & Ryo Nakagawa

  3. Project for Cancer Epigenomics, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan

    Reo Maruyama

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  1. Takahiro Seimiya
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Contributions

TS and MO designed the research. TS, TI, ET, KS, and CS performed majority of the experiments. MM and RN obtained clinical samples. TS, MO, and RM analyzed the data. TS, MO, and KK wrote the manuscript.

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Correspondence to Motoyuki Otsuka.

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Seimiya, T., Otsuka, M., Iwata, T. et al. Aberrant expression of a novel circular RNA in pancreatic cancer. J Hum Genet 66, 181–191 (2021). https://doi.org/10.1038/s10038-020-00826-5

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