Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H

Yuki Shibayama; Kazuo Takahashi; Hisateru Yamaguchi; Jun Yasuda; Daisuke Yamazaki; Asadur Rahman; Takayuki Fujimori; Yoshihide Fujisawa; Shinji Takai; Toru Furukawa; Tsutomu Nakagawa; Hiroyuki Ohsaki; Hideki Kobara; Jing Hao Wong; Tsutomu Masaki; Yukio Yuzawa; Hideyasu Kiyomoto; Shinichi Yachida; Akihiro Fujimoto; Akira Nishiyama

doi:10.1038/s42003-020-01434-x

Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H

Yuki Shibayama, Kazuo Takahashi, Hisateru Yamaguchi, Jun Yasuda, Daisuke Yamazaki, Asadur Rahman, Takayuki Fujimori, Yoshihide Fujisawa, Shinji Takai, Toru Furukawa, Tsutomu Nakagawa, Hiroyuki Ohsaki, Hideki Kobara, Jing Hao Wong, Tsutomu Masaki, Yukio Yuzawa, Hideyasu Kiyomoto, Shinichi Yachida, Akihiro Fujimoto, Akira Nishiyama

Research output: Contribution to journal › Article › peer-review

Abstract

(Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.

Original language	English
Article number	724
Journal	Communications biology
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s42003-020-01434-x
Publication status	Published - 12-2020

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Medicine (miscellaneous)
Medicine(all)

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Shibayama, Y., Takahashi, K., Yamaguchi, H., Yasuda, J., Yamazaki, D., Rahman, A., Fujimori, T., Fujisawa, Y., Takai, S., Furukawa, T., Nakagawa, T., Ohsaki, H., Kobara, H., Wong, J. H., Masaki, T., Yuzawa, Y., Kiyomoto, H., Yachida, S., Fujimoto, A., & Nishiyama, A. (2020). Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H. Communications biology, 3(1), [724]. https://doi.org/10.1038/s42003-020-01434-x

Shibayama, Yuki ; Takahashi, Kazuo ; Yamaguchi, Hisateru ; Yasuda, Jun ; Yamazaki, Daisuke ; Rahman, Asadur ; Fujimori, Takayuki ; Fujisawa, Yoshihide ; Takai, Shinji ; Furukawa, Toru ; Nakagawa, Tsutomu ; Ohsaki, Hiroyuki ; Kobara, Hideki ; Wong, Jing Hao ; Masaki, Tsutomu ; Yuzawa, Yukio ; Kiyomoto, Hideyasu ; Yachida, Shinichi ; Fujimoto, Akihiro ; Nishiyama, Akira. / Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H. In: Communications biology. 2020 ; Vol. 3, No. 1.

@article{0a5721e6b83b4f5198fbe42a1d4d4871,

title = "Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H",

abstract = "(Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.",

author = "Yuki Shibayama and Kazuo Takahashi and Hisateru Yamaguchi and Jun Yasuda and Daisuke Yamazaki and Asadur Rahman and Takayuki Fujimori and Yoshihide Fujisawa and Shinji Takai and Toru Furukawa and Tsutomu Nakagawa and Hiroyuki Ohsaki and Hideki Kobara and Wong, {Jing Hao} and Tsutomu Masaki and Yukio Yuzawa and Hideyasu Kiyomoto and Shinichi Yachida and Akihiro Fujimoto and Akira Nishiyama",

note = "Funding Information: We are grateful to Mr Kouichi Yube (Division of Research Instrument and Equipment, Kagawa University) for handling Flow Cytometry and ABI PRISM 3100 Genetic Analyzer, Mr Toru Matsunaga (Department of pathology, Kagawa University Hospital) for performing Papanicolaou stain, Ms Miho Seki (Department of Pharmacology, Faculty of Medicine, Kagawa University) for help with the western blotting and agarose gel electrophoresis, and Mr Yuji Yokota (Department of Pharmacology, Faculty of Medicine, Kagawa University) for taking care of the immunodeficient mice. Mr Koichi Ishiguro (AXIOHELIX Co. Ltd., Okinawa, Japan) also helped to perform the analysis of the human whole-genome sequence. Ms Kanako Ohtsuki created the images of Fig. 7. We also thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript. This study was supported by Grants-in-Aid for Scientific Research (16K14610 and 19K07690 to Y.S. and 18H03191 to A.N.) from the Ministry of Education, Science and Culture of Japan and from the Tokyo Biomarker Innovation Research Associate (TOBIRA), the Hoansha Foundation and Alumni Association of Kagawa University (Sanjukai).",

year = "2020",

month = dec,

doi = "10.1038/s42003-020-01434-x",

language = "English",

volume = "3",

journal = "Communications Biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

Shibayama, Y, Takahashi, K, Yamaguchi, H, Yasuda, J, Yamazaki, D, Rahman, A, Fujimori, T, Fujisawa, Y, Takai, S, Furukawa, T, Nakagawa, T, Ohsaki, H, Kobara, H, Wong, JH, Masaki, T, Yuzawa, Y, Kiyomoto, H, Yachida, S, Fujimoto, A & Nishiyama, A 2020, 'Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H', Communications biology, vol. 3, no. 1, 724. https://doi.org/10.1038/s42003-020-01434-x

Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H. / Shibayama, Yuki; Takahashi, Kazuo; Yamaguchi, Hisateru; Yasuda, Jun; Yamazaki, Daisuke; Rahman, Asadur; Fujimori, Takayuki; Fujisawa, Yoshihide; Takai, Shinji; Furukawa, Toru; Nakagawa, Tsutomu; Ohsaki, Hiroyuki; Kobara, Hideki; Wong, Jing Hao; Masaki, Tsutomu; Yuzawa, Yukio; Kiyomoto, Hideyasu; Yachida, Shinichi; Fujimoto, Akihiro; Nishiyama, Akira.

In: Communications biology, Vol. 3, No. 1, 724, 12.2020.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H

AU - Shibayama, Yuki

AU - Takahashi, Kazuo

AU - Yamaguchi, Hisateru

AU - Yasuda, Jun

AU - Yamazaki, Daisuke

AU - Rahman, Asadur

AU - Fujimori, Takayuki

AU - Fujisawa, Yoshihide

AU - Takai, Shinji

AU - Furukawa, Toru

AU - Nakagawa, Tsutomu

AU - Ohsaki, Hiroyuki

AU - Kobara, Hideki

AU - Wong, Jing Hao

AU - Masaki, Tsutomu

AU - Yuzawa, Yukio

AU - Kiyomoto, Hideyasu

AU - Yachida, Shinichi

AU - Fujimoto, Akihiro

AU - Nishiyama, Akira

N1 - Funding Information: We are grateful to Mr Kouichi Yube (Division of Research Instrument and Equipment, Kagawa University) for handling Flow Cytometry and ABI PRISM 3100 Genetic Analyzer, Mr Toru Matsunaga (Department of pathology, Kagawa University Hospital) for performing Papanicolaou stain, Ms Miho Seki (Department of Pharmacology, Faculty of Medicine, Kagawa University) for help with the western blotting and agarose gel electrophoresis, and Mr Yuji Yokota (Department of Pharmacology, Faculty of Medicine, Kagawa University) for taking care of the immunodeficient mice. Mr Koichi Ishiguro (AXIOHELIX Co. Ltd., Okinawa, Japan) also helped to perform the analysis of the human whole-genome sequence. Ms Kanako Ohtsuki created the images of Fig. 7. We also thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript. This study was supported by Grants-in-Aid for Scientific Research (16K14610 and 19K07690 to Y.S. and 18H03191 to A.N.) from the Ministry of Education, Science and Culture of Japan and from the Tokyo Biomarker Innovation Research Associate (TOBIRA), the Hoansha Foundation and Alumni Association of Kagawa University (Sanjukai).

PY - 2020/12

Y1 - 2020/12

N2 - (Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.

AB - (Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.

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U2 - 10.1038/s42003-020-01434-x

DO - 10.1038/s42003-020-01434-x

M3 - Article

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AN - SCOPUS:85096697218

VL - 3

JO - Communications Biology

JF - Communications Biology

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