Abstract
Calponin 3 (CNN3) is known to serve a role in certain types of cancer, such as gastric cancer and colorectal cancer. The present study investigated the clinical significance of CNN3 in non-small cell lung cancer (NSCLC) by evaluating its expression profile and relationship with disease prognosis using the Gene Expression Omnibus repository, Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Kaplan-Meier plotter analysis. CNN3 mRNA expression was measured using reverse transcription-quantitative PCR, while the protein expression level was measured using western blot analysis. Cell proliferation, cell cycle and apoptosis, and migration and invasion were analyzed using MTS assay, flow cytometry and Transwell assays, respectively. These results revealed that CNN3 mRNA expression was downregulated in NSCLC tissues compared with that in normal tissues. Additionally, CNN3 expression had a high diagnostic value based on the GSE2514 dataset and the data from The Cancer Genome Atlas and the Genotype Tissue Expression database, whereas it had a low diagnostic value based on the GSE10072 dataset. Furthermore, CNN3 expression was associated with survival in patients with lung adenocarcinoma (LUAD), whereas it was not associated with survival in patients with lung squamous cell carcinoma (LUSC) according to the Kaplan-Meier plotter results. According to the data from GEPIA2, and the GSE72094, GSE41271 and GSE31210 datasets, CNN3 expression was not associated with the prognosis of patients with LUAD and LUSC. The mRNA and protein expression levels of CNN3 were lower in two NSCLC cell lines (A549 and SK-MES-1) than in a human bronchial epithelial cell line (BEAS-2B). CNN3 overexpression suppressed cell proliferation, migration and invasion, induced G1-phase arrest, promoted apoptosis and suppressed PI3K/AKT signaling pathway activation in the NSCLC cell lines, whereas CNN3 overexpression had no effect on cell morphology. In conclusion, CNN3 suppressed the proliferation and metastasis of NSCLC cells by downregulating the PI3K/AKT signaling pathway, making it a potential therapeutic target in this disease.