清脆的
前列腺癌
表观遗传学
PTEN公司
生物
癌症研究
转移
基因
色丛
癌症
Cas9
计算生物学
遗传学
PI3K/AKT/mTOR通路
PCA3系列
细胞凋亡
作者
Huiqiang Cai,Bin Zhang,Johanne Ahrenfeldt,Justin V. Joseph,Maria Riedel,Zongliang Gao,Simon Nørskov Thomsen,Ditte S. Christensen,Rasmus O. Bak,Henrik Hager,Mikkel Holm Vendelbo,Xin Gao,Nicolai J. Birkbak,Martin K. Thomsen
标识
DOI:10.1038/s41467-024-46370-0
摘要
Abstract Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C. Depleting Odam and Cabs1 in this region prevents metastasis. Notably, the gene expression signatures, resulting from our study, predict progression-free and overall survival and distinguish primary and metastatic human prostate cancer. This study emphasizes positive genetic interactions between classical tumor suppressor genes and epigenetic modulators in metastatic PCa progression, offering insights into potential treatments.
科研通智能强力驱动
Strongly Powered by AbleSci AI