MNX1 facilitates the malignant progress of lung adenocarcinoma through transcriptionally upregulating CCDC34.

ABSTRACT

Lung adenocarcinoma (LUAD) represents the most prevalent subtype of lung cancer and typically has high incidence and fatality rates. Motor neuron and pancreas homeobox 1 (MNX1) and coiled-coil domain-containing 34 (CCDC34) serve as oncogenes in multiple types of cancer. However, their role in LUAD remains to be elucidated. In the present study, bioinformatics analysis and LUAD cell lines were adopted to examine the expression of MNX1 and CCDC34. The proliferation, migration and invasion abilities of A549 cells were determined using Cell Counting Kit-8, colony formation, wound-healing and Transwell assay, and flow cytometry was conducted to assess cell cycle distribution and apoptosis. The interaction between MNX1 and CCDC34 was verified by luciferase reporter and chromatin immunoprecipitation assays. In addition, an in vivo animal model of LUAD was established for validation. The results demonstrated that both MNX1 and CCDC34 were upregulated in LUAD cell lines. MNX1 knockdown significantly suppressed cell proliferation, migration and invasion, hindered cell cycle progression and promoted cell apoptosis in vitro and inhibited tumor growth in vivo. However, the antitumor effect of MNX1 knockdown was weakened by simultaneous CCDC34 overexpression in vitro. In terms of mechanism, MNX1 was demonstrated to directly bind to the CCDC34 promoter and transcriptionally activate CCDC34 expression. In conclusion, the present study highlighted a critical role of the MNX1/CCDC34 axis in regulating LUAD progression, providing novel therapeutic targets for LUAD treatment.