Oncogene ( IF 6.9 ) Pub Date : 2023-11-10 , DOI: 10.1038/s41388-023-02883-4 Weiwei Chen 1 , Fei Wang 1 , Xinyuan Yu 2 , Jingjing Qi 3 , Hongliang Dong 1 , Bingjie Cui 1 , Qian Zhang 4 , Yan Wu 1, 2 , Jiajia An 5 , Na Ni 1 , Cuilan Liu 1 , Yuchen Han 5 , Shuo Zhang 1, 6 , Clemens A Schmitt 7, 8, 9, 10, 11 , Jiong Deng 1 , Yong Yu 3 , Jing Du 1, 2, 6
Non-coding RNAs are responsible for oncogenesis and the development of stemness features, including multidrug resistance and metastasis, in various cancers. Expression of lncRNA MIR31HG in lung cancer tissues and peripheral sera of lung cancer patients were remarkably higher than that of healthy individuals and indicated a poor prognosis. Functional analysis showed that MIR31HG fosters stemness-associated malignant features of non-small cell lung cancer cells. Further mechanistic investigation revealed that MIR31HG modulated GLI2 expression via WDR5/MLL3/P300 complex-mediated H3K4me and H3K27Ace modification. In vivo MIR31HG repression with an antisense oligonucleotide attenuated tumor growth and distal organ metastasis, whereas MIR31HG promotion remarkably encouraged cellular invasion in lung and liver tissues. Our data suggested that MIR31HG is a potential diagnostic indicator and druggable therapeutic target to facilitate multiple strategic treatments for lung cancer patients.
中文翻译:
LncRNA MIR31HG 通过 H3K4me1 和 H3K27Ace 介导的 GLI2 表达促进非小细胞肺癌的干细胞恶性特征
非编码 RNA 负责各种癌症的肿瘤发生和干性特征的发展,包括多药耐药性和转移。肺癌患者肺癌组织和外周血清中lncRNA MIR31HG的表达显着高于健康个体,提示预后不良。功能分析表明,MIR31HG 促进非小细胞肺癌细胞的干性相关恶性特征。进一步的机制研究表明,MIR31HG 通过 WDR5/MLL3/P300 复合物介导的 H3K4me 和 H3K27Ace 修饰来调节 GLI2 表达。在体内,用反义寡核苷酸抑制 MIR31HG 可减弱肿瘤生长和远端器官转移,而 MIR31HG 促进则显着促进肺和肝组织中的细胞侵袭。我们的数据表明,MIR31HG 是一种潜在的诊断指标和药物治疗靶点,可促进肺癌患者的多种战略治疗。