Yang Lijun, Li Jiping
Medical College of Tibet University, Lhasa, 850000, China.
West China School of Nursing, Sichuan University/West China Hospital, Sichuan University, No.37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan Province, China.
Clin Exp Metastasis. 2025 Apr 18;42(3):26. doi: 10.1007/s10585-025-10340-7.
This study investigates crucial genes involved in lung cancer metastasis and their interactions within a Competitive endogenous RNA (ceRNA) regulatory network using comprehensive transcriptomic data from the TCGA and GEO databases. Differential expression analysis identified ten genes associated with lung cancer metastasis, with Glypican-3 (GPC3) emerging as a key mRNA through survival analysis. A ceRNA network involving GPC3, hsa-miR-135b-3p, and FTLP3 was constructed and validated in both cellular and animal models, elucidating their roles in cell migration, invasion, and tumorigenic potential. The analysis confirmed the significance of key genes like GPC3, with the FTLP3/hsa-miR-135b-3p/GPC3 axis playing a fundamental role in lung cancer progression. Additionally, the study identified correlations between GPC3 expression, immune cell infiltration and immune checkpoints, underscoring its impact on the immune landscape of lung cancer. Overexpression of FTLP3 effectively suppressed the migratory, invasive, and metastatic abilities of lung cancer cells, demonstrating the pivotal role of the FTLP3/hsa-miR-135b-3p/GPC3 ceRNA network in modulating tumor progression and immune responses. These results underscore its potential as a therapeutic target for managing lung cancer metastasis.
本研究利用来自TCGA和GEO数据库的全面转录组数据，调查参与肺癌转移的关键基因及其在竞争性内源性RNA（ceRNA）调控网络中的相互作用。差异表达分析确定了十个与肺癌转移相关的基因，通过生存分析发现磷脂酰肌醇蛋白聚糖-3（GPC3）作为关键mRNA出现。构建了一个涉及GPC3、hsa-miR-135b-3p和FTLP3的ceRNA网络，并在细胞和动物模型中进行了验证，阐明了它们在细胞迁移、侵袭和致瘤潜力中的作用。分析证实了GPC3等关键基因的重要性，FTLP3/hsa-miR-135b-3p/GPC3轴在肺癌进展中起基本作用。此外，该研究确定了GPC3表达、免疫细胞浸润和免疫检查点之间的相关性，强调了其对肺癌免疫格局的影响。FTLP3的过表达有效抑制了肺癌细胞的迁移、侵袭和转移能力，证明了FTLP3/hsa-miR-135b-3p/GPC3 ceRNA网络在调节肿瘤进展和免疫反应中的关键作用。这些结果强调了其作为治疗肺癌转移靶点的潜力。
