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

研究成果: Article査読

抄録

(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.

本文言語English
論文番号724
ジャーナルCommunications biology
3
1
DOI
出版ステータス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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