拼接因子
卵巢癌
癌症研究
选择性拼接
癌症
医学
生物
内科学
生物化学
基因
信使核糖核酸
作者
Xihan Liu,Jiaojiao Zhang,Zixiang Wang,Mingyao Yan,Mingfang Xu,Gaoyuan Li,Victoria О. Shender,Jian‐Jun Wei,Jianqiao Li,Changshun Shao,Shiqian Zhang,Beihua Kong,Kun Song,Zhaojian Liu
标识
DOI:10.1002/advs.202306229
摘要
Abstract Splicing factor polyglutamine binding protein‐1 (PQBP1) is abundantly expressed in the central nervous system during development, and mutations in the gene cause intellectual disability. However, the roles of PQBP1 in cancer progression remain largely unknown. Here, it is shown that PQBP1 overexpression promotes tumor progression and indicates worse prognosis in ovarian cancer. Integrative analysis of spyCLIP‐seq and RNA‐seq data reveals that PQBP1 preferentially binds to exon regions and modulates exon skipping. Mechanistically, it is shown that PQBP1 regulates the splicing of genes related to the apoptotic signaling pathway, including BAX. PQBP1 promotes BAX exon 2 skipping to generate a truncated isoform that undergoes degradation by nonsense‐mediated mRNA decay, thus making cancer cells resistant to apoptosis. In contrast, PQBP1 depletion or splice‐switching antisense oligonucleotides promote exon 2 inclusion and thus increase BAX expression, leading to inhibition of tumor growth. Together, the results demonstrate an oncogenic role of PQBP1 in ovarian cancer and suggest that targeting the aberrant splicing mediated by PQBP1 has therapeutic potential in cancer treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI