Interplay of GPC3, Hsa-miR-135b-3p, and FTLP3 in lung cancer metastasis

Abstract

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.

Keywords: FTLP3; GPC3; Immune checkpoint; Lung cancer metastasis; ceRNA regulatory network; miR-135b-3p.