New insights into the function and mechanisms of piRNA PMLCPIR in promoting PM2.5-induced lung cancer

作者：Lin Xu, Wanli Ma, Xiaoyu Huo, Jiao Luo, Ruoxi Li, Xiaoxiao Zhu, Xiangbin Kong, Kunming Zhao, Yuan Jin, Meihua Zhang, X. Li, Ling Wang, Wei Han, Dianke Yu · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.08.029 · 被引用次数：41 · 研究领域：PI3K/AKT/mTOR signaling in cancer、MicroRNA in disease regulation、Protein Tyrosine Phosphatases

• PMLCPIR is up-regulated in PM 2.5 -induced malignant transformation and lung tumors of human patients. • The PMLCPIR promotes lung cancer progression by targeting ITGB1. • Increased ITGB1 expression activates PI3K/AKT axis. • PMLCPIR upregulates ITGB1 expression by disturbing the interaction between NCL and ITGB1. • Inhibition of PMLCPIR diminishes lung cancer growth in vivo . Extensive studies have established the correlation between long-term PM 2.5 exposure and lung cancer, yet the mechanisms underlying this association remain poorly understood. PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, serve important roles in various diseases. However, their biological function and mechanism in PM 2.5 -induced lung cancer have not been thoroughly investigated. We aimed to explore the oncogenic role of piRNA in lung cancer induced by PM 2.5 exposure, as well as the underlying mechanisms. We conducted a PM 2.5 -induced human lung epithelial cell malignant transformation model. Human samples were used to further verify the finding. In vitro proliferation, migration, and invasion assays were performed to study the function of piRNA. RNA-sequencing was used to elucidate the the mechanisms of how piRNA mediates cell functions. PiRNA pull-down and computational docking analysis were conducted to identify proteins that binding to piRNA. In vivo experiments were used to explore whether inhibition of PMLCPIR could have a therapeutic effect on lung cancer. We iden...