Exosomes overexpressing CDC73 inhibit malignant progression of Lung adenocarcinoma

Abstract

Abstract Background: Early diagnosis and treatment of LUAD remains the focus of current research. The aim of this research is to assess the influence of CDC73 on the progression of LUAD malignancy and its potential as a biomarker for diagnosing LUAD. Furthermore, CDC73 may have the potential to be utilized in the treatment of LUAD. Methods: By applying both electron microscopy (TEM) and nanoparticle tracking technology (NTA), we were able to analyze and validate the purity of the exosomes, and screen outthe biomarker for diagnosing LUAD via protein group analysis and Western immunoblotting experiments. In vitro experiments were conducted to investigate the impact of CDC73 on the malignant behavior of LUAD cells. We then conducted co-immunoprecipitation and mass spectrometry analysis experiments to investigate the effect of CDC73 on the PI3K/AKT signaling pathway. To further assess the inhibitory effect of CDC73 on LUAD progression, we conducted in vivo experiments (xenograft tumor growth). Lastly, ultracentrifugation was utilized to isolate exosomes from the supernatant of LUAD cells in order to gain more information regarding the mechanism of action of CDC73 in these exosomes. Results: The expression of CDC73 was markedly lower in exosomes from the plasma of LUAD patients than in healthy human plasma exosomes. In vitro and in vivo research has demonstrated that CDC73 forms a complex with the cancer suppressor protein PTEN via CTNNB1, thereby inhibiting the PI3K/AKT signaling pathway and diminishing malignant behavior in LUAD. Furthermore, LUAD cells transfected with CDC73 were found to reduce the malignant behavior of exosomes secreted by these cells, including their ability to promote growth and metastasis. Conclusions: CDC73 is a tumor suppressor gene for LUAD and could be used as a diagnostic marker for the disease. Additionally, we observed an increase in CDC73 expression in exosomes secreted by LUAD cells overexpressing CDC73 and a decrease in their ability to promote the malignant phenotype of normal lung cells. Exosomes expressing the gene CDC73 could potentially open the door to a new therapeutic approach for treating LUAD.