(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.

肾素原受体[（P）RR]在多种疾病中起作用，例如心血管和肾脏疾病以及癌症。胰腺导管腺癌（PDAC）中最常见的胰腺癌是异常（P）RR表达。在这里我们显示（P）RR的异常表达是否直接导致人胰腺导管上皮（HPDE）细胞中的基因组不稳定。表达（P）RR的HPDE细胞显示出明显的细胞异型性。全基因组测序表明，异常（P）RR表达在基因组水平上诱导了大量的点突变和结构变异。表达（P）RR的细胞群体具有形成肿瘤的能力，既显示以独特核体为特征的非典型核，又显示染色体异常。（P）RR过表达上调SWItch /不可发酵蔗糖（SWI / SNF）相关的 通过直接的分子相互作用，与基质相关的，染色质a家族成员的肌动蛋白依赖性调节剂（SMARCA5）相互作用，导致多个基因组稳定途径的失败。这些数据表明异常（P）RR表达有助于PDAC的早期致癌作用。