An Zhiyuan, Yao Ningning, Su Wenzhong, Zhang Weiyang, Yang Junting, Guo Qinping, Zhang Congqiao, Tian Pan, Wan Neng, Wu Congcong, Huang Xiang, Song Guohua, Jia Junting, Ren Laifeng
Central Laboratory, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital/Chinese Academy of Medical Sciences, Taiyuan, 030001, Shanxi, China.
Department of Basic Medical Sciences , Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
Sci Rep. 2025 Jul 2;15(1):22576. doi: 10.1038/s41598-025-06219-y.
Lung cancer is the leading cause of cancer-related mortality, with a notably low five-year survival rate due to the limited availability of effective treatments. Monoubiquitination of histone H2B at lysine 120(uH2B) exerts a tumor-suppressive effect in cancer through multiple mechanisms, including the regulation of transcriptional activity and DNA damage response. Ring Finger Protein 20 (RNF20), a key E3 ubiquitin ligase, plays a central role in this process. However, the role of RNF20 in lung adenocarcinoma (LUAD) progression is unknown. In this study, the functional characterization of the role and molecular mechanism of LUAD were examined using a series of biological and cellular approaches in vitro and in vivo. Our work shows the expression of uH2B is significantly reduced in LUAD patients and is correlated with prognosis. Similarly, RNF20 expression is also markedly decreased in LUAD. Knockdown of RNF20 promoted the proliferation and migration of A549 cells while simultaneously decreasing uH2B expression. Additionally, RNF20 knockdown impaired the DNA damage repair capacity of LUAD cells. RNF20-silenced A549 cells exhibited heightened sensitivity to both the Cisplatin and PARP inhibitor Olaparib. These findings provide an important foundation for further understanding the molecular mechanisms of lung adenocarcinoma and developing new treatment strategies.
肺癌是癌症相关死亡的主要原因，由于有效治疗方法有限，其五年生存率极低。组蛋白H2B赖氨酸120位点的单泛素化（uH2B）通过多种机制在癌症中发挥肿瘤抑制作用，包括调节转录活性和DNA损伤反应。指环蛋白20（RNF20）是一种关键的E3泛素连接酶，在这一过程中起核心作用。然而，RNF20在肺腺癌（LUAD）进展中的作用尚不清楚。在本研究中，我们使用一系列体外和体内的生物学和细胞方法，研究了LUAD的作用及其分子机制的功能特征。我们的研究表明，uH2B在LUAD患者中的表达显著降低，且与预后相关。同样，RNF20在LUAD中的表达也明显降低。敲低RNF20可促进A549细胞的增殖和迁移，同时降低uH2B的表达。此外，敲低RNF20会损害LUAD细胞的DNA损伤修复能力。RNF20沉默的A549细胞对顺铂和PARP抑制剂奥拉帕尼均表现出更高的敏感性。这些发现为进一步了解肺腺癌的分子机制和开发新的治疗策略提供了重要基础。
