EVI5 Drives Lung Adenocarcinoma Progression through Modulation of the ERK1/2-c-Myc Signaling Axis

Lung adenocarcinoma (LUAD) remains a lethal disease worldwide with a poor prognosis. The ecotropic viral integration site 5 (EVI5) is a crucial oncogene and mediator of cell division processes, and it extensively participates in tumorigenesis and progression. However, the role of EVI5 in LUAD progression remains elusive. This study aimed to further explore the underlying mechanisms of EVI5's involvement in LUAD development.

The GEO database was employed to investigate the expression of EVI5 in LUAD and normal tissues, while the Kaplan-Meier Plotter database was utilized to assess its correlation with patient prognosis. Stable cell lines with EVI5 knockout and overexpression were constructed, and Western blotting was performed to detect EVI5 protein expression levels to validate the successful establishment of the stable cell lines. The abilities of proliferation, invasion, and migration of LUAD cells after transfection were analyzed using CCK-8, colony formation, transwell, and wound healing assays. Western blotting, immunofluorescence, and qRT-PCR were further carried out to measure the protein and mRNA expression levels associated with the ERK1/2-c-Myc signaling pathway. Finally, functional rescue experiments were performed on LUAD cells to further explore and verify the signaling pathway.

EVI5 was found to be highly expressed in lung adenocarcinoma tissues and correlated with poor prognosis. EVI5 overexpression promoted the malignant behavior of lung adeno-carcinoma, whereas its knockout produced the opposite effect. Mechanistically, ERK1/2-c-Myc, the key signaling pathway in the malignant progression of LUAD, was further validated by an ERK1/2 pathway inhibitor.

Our study demonstrated for the first time that EVI5 promotes malignant progression through the activation of the ERK1/2-c-Myc signaling axis, providing new insights into the pathogenesis of LUAD.