香烟烟雾提取物通过上调PRMT6促进非小细胞肺癌的上皮-间质转化
Cigarette Smoke Extract Promotes Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer by Upregulating PRMT6.
作者
作者单位
- Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.
摘要
中文
非小细胞肺癌（NSCLC）是全球癌症相关死亡的主要原因。香烟烟雾提取物（CSE）是驱动NSCLC进展的主要环境因素，但其潜在分子机制尚未完全阐明。蛋白精氨酸甲基转移酶6（PRMT6）参与包括NSCLC在内的多种恶性肿瘤，上皮-间质转化（EMT）导致该疾病的转移和不良预后。然而，PRMT6在CSE诱导的NSCLC进展中的作用尚未阐明。通过裸鼠皮下异种移植模型和H1299细胞体外实验评估CSE暴露下的NSCLC进展。通过免疫组织化学、CCK-8、伤口愈合、Transwell、免疫荧光、qRT-PCR和western blotting评估肿瘤生长和分子改变。CSE暴露增强了H1299细胞体外增殖、迁移和侵袭，并促进了体内异种移植肿瘤的生长。这伴随着PRMT6及其效应分子H3R2me2a表达上调，间充质标志物（N-cadherin、MMP2、MMP9、vimentin）和转录因子（Snail、TWIST1）升高，以及PI3K p85、Akt和mTOR磷酸化增加。值得注意的是，所有CSE诱导的效应均被PRMT6抑制剂EPZ020411消除。CSE通过上调PRMT6促进NSCLC进展，导致PI3K/Akt/mTOR激活和EMT诱导。这些发现凸显了PRMT6作为NSCLC潜在治疗靶点的价值。
English
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. Cigarette smoke extract (CSE) is a major environmental factor driving NSCLC progression, yet the underlying molecular mechanisms remain incompletely understood. Protein arginine methyltransferase 6 (PRMT6) is implicated in various malignancies, including NSCLC, and epithelial-mesenchymal transition (EMT) contributes to metastasis and poor prognosis in this disease. However, the role of PRMT6 in CSE-induced NSCLC progression has not been elucidated. NSCLC progression under CSE exposure was assessed using a subcutaneous xenograft model in nude mice and in vitro assays in H1299 cells. Tumor growth and molecular alterations were evaluated by immunohistochemistry, CCK-8, wound healing, Transwell, immunofluorescence, qRT-PCR, and western blotting. CSE exposure enhanced H1299 cell proliferation, migration, and invasion in vitro and promoted xenograft tumor growth in vivo. This was accompanied by upregulated expression of PRMT6 and its effector H3R2me2a, elevated mesenchymal markers (N-cadherin, MMP2, MMP9, vimentin), and transcription factors (Snail, TWIST1), and increased phosphorylation of PI3K p85, Akt, and mTOR. Notably, all CSE-induced effects were abrogated by the PRMT6 inhibitor EPZ020411. CSE promotes NSCLC progression by upregulating PRMT6, leading to PI3K/Akt/mTOR activation and EMT induction. These findings highlight PRMT6 as a potential therapeutic target in NSCLC.
分类与指标
- 研究类型
- 基础研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 2.6
- 新锐分区
- 4区