MAPK/ERK通路
脑转移
转移
癌症研究
肺癌
医学
基因沉默
车站3
信号转导
癌症
免疫学
生物
病理
内科学
细胞生物学
生物化学
基因
作者
Tung-Yu Tiong,M. Ete Chan,Chun-Hua Wang,Vijesh Kumar Yadav,Narpati Wesa Pikatan,Iat-Hang Fong,Chi‐Tai Yeh,Kuang-Tai Kuo,Wen‐Chien Huang
出处
期刊:Life Sciences
[Elsevier]
日期:2023-09-01
卷期号:329: 121945-121945
被引量:4
标识
DOI:10.1016/j.lfs.2023.121945
摘要
Brain metastasis affects 20-40 % of lung cancer patients, severely diminishing their quality of life. This research focuses on miR-21, overexpressed in these patients and inversely associated with DGKB in the ERK/STAT3 pathway, suggesting a dysregulated pathway with therapeutic potential.The objective was to investigate miR-21's role in lung cancer patients with brain metastases and whether targeting this pathway could improve treatment outcomes. We also examined the miR-21 content in tumor spheres-derived extracellular vesicles (EVs) and their influence on ERK/STAT3 signaling and metastasis.Tumor spheres were created from metastatic lung cancer cells. We studied miR-21 levels in these spheres, their impact on macrophage polarization, and the transition of nonmetastatic lung cancer cells. Furthermore, we analyzed miR-21 content in EVs derived from these spheres and their effect on ERK/STAT3 signaling and metastasis potential.We found tumor spheres had high miR-21 levels, promoting macrophage polarization and, epithelial-mesenchymal transition. These spheres-derived EVs, enriched with miR-21, accelerated ERK/STAT3 signaling and metastasis. Silencing miR-21 and inhibiting ERK signaling with ulixertinib notably mitigated these effects. Moreover, ulixertinib reduced brain metastasis incidence and increased survival in a mouse model and led to reduced tumor sphere generation and miR-21 levels in EVs.Our study highlights the exacerbation of lung-to-brain metastasis via miR-21-rich EV secretion. This underlines the therapeutic promise of targeting the miR-21/ERK/STAT3 pathway with ulixertinib for managing brain metastasis from lung cancer.
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