Plasmacytoma variant translocation 1 stabilized by EIF4A3 promoted malignant biological behaviors of lung adenocarcinoma by generating circular RNA LMNB2.

Increasing evidence suggests that plasmacytoma variant translocation 1 (PVT1) plays a vital role in the development of multiple tumors including lung adenocarcinoma (LUAD). Eukaryotic initiation factor 4A-3 (EIF4A3) is considered a key factor in human cancers. However, the role and potential mechanism of PVT1 combined with EIF4A3 in LUAD remain unclear. This study investigated the effects and regulatory mechanisms of PVT1, EIF4A3, and circLMNB2 on the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells (H1299 and HCC827 cells) The expression level, diagnostic value and prognostic significance of PVT1, EIF4A3, and circLMNB2 were assessed, and enrichment analysis was performed using R package. Rescue experiments and a xenograft model were used to validate the PVT1/EIF4A3/circLMNB2 axis in LUAD. PVT1 and EIF4A3 were upregulated and indicated poor prognosis in LUAD. Knockdown of PVT1 and EIF4A3 suppressed LUAD cell proliferation, migration, invasion, and EMT. Mechanistically, PVT1 was stabilized by EIF4A3. PVT1 could recruit EIF4A3 to promote circLMNB2 expression. Rescue experiments indicated that circLMNB2 overexpression could reverse the reduced behavior caused by PVT1 or EIF4A3 knockdown. Enrichment analysis showed that PVT1/EIF4A3/circLMNB2 may regulate LUAD development by participating in ribosome biogenesis and spliceosome formation. Our findings demonstrate that PVT1/EIF4A3/circLMNB2 enhances the malignant behaviors of LUAD cells, providing a novel perspective for the clinical treatment of LUAD.