Tan Liangting, Xiang Xuesong, Qian Qiyi, Zhang Qikun, Xu Qiuran, Qiu Wenhong, Zheng Xiaoliang
Zhejiang Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine, School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, China.
Department of Immunology, Jianghan University, School of Medicine, Wuhan, China.
Medicine (Baltimore). 2025 Jul 18;104(29):e43483. doi: 10.1097/MD.0000000000043483.
Lung cancer is one of the most prevalent malignancies worldwide, and the metastasis of nonsmall cell lung cancer often leads to rapid deterioration of patient conditions, with brain metastasis (BM) being the most detrimental. The mechanisms underlying lung cancer brain metastasis remain incompletely understood.
This study aimed to elucidate the molecular mechanisms of lung cancer brain metastasis and identify potential biomarkers and therapeutic targets.
The high invasiveness of H1975-BM51 cells was verified using Western blotting, cell invasion assays, and the establishment of an nonsmall cell lung cancer brain metastasis mouse model. Transcriptome sequencing of H1975 and H1975-BM51 cells was conducted, followed by Least Absolute Shrinkage and Selection Operator regression and single-gene Gene Set Enrichment Analysis to screen key genes. Quantitative real-time PCR and Western blotting were employed to detect the expression levels of the AGO3 gene in H1975-BM51 cells.
Transcriptomic analysis revealed that the AGO3 gene contributes to lung cancer brain metastasis by negatively regulating hormone metabolic processes. Compared with parental H1975 cells, both mRNA and protein expression levels of AGO3 were significantly upregulated in highly invasive H1975-BM51 cells.
This study identifies AGO3 as a potential biomarker and therapeutic target for lung cancer brain metastasis.
肺癌是全球最常见的恶性肿瘤之一,非小细胞肺癌的转移常导致患者病情迅速恶化,其中脑转移最为严重。肺癌脑转移的潜在机制仍未完全明确。
本研究旨在阐明肺癌脑转移的分子机制,并确定潜在的生物标志物和治疗靶点。
通过蛋白质印迹法、细胞侵袭实验以及建立非小细胞肺癌脑转移小鼠模型,验证H1975-BM51细胞的高侵袭性。对H1975和H1975-BM51细胞进行转录组测序,随后采用最小绝对收缩和选择算子回归以及单基因基因集富集分析来筛选关键基因。运用定量实时聚合酶链反应和蛋白质印迹法检测H1975-BM51细胞中AGO3基因的表达水平。
转录组分析表明,AGO3基因通过负调控激素代谢过程促进肺癌脑转移。与亲本H1975细胞相比,高侵袭性的H1975-BM51细胞中AGO3的mRNA和蛋白质表达水平均显著上调。
本研究确定AGO3为肺癌脑转移的潜在生物标志物和治疗靶点。