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: ジャーナルへの寄稿学術論文査読

6 被引用数 (Scopus)

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.

本文言語英語
論文番号724
ジャーナルCommunications biology
3
1
DOI
出版ステータス出版済み - 12-2020

All Science Journal Classification (ASJC) codes

  • 医学(その他)
  • 生化学、遺伝学、分子生物学一般
  • 農業および生物科学一般

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