MTAP deficiency in lung cancer cells enhances proliferation and migration and increases vulnerability to bone metastasis

Abstract

Lung cancer continues to be the leading cause of cancer-related death worldwide. The advent of molecular targeted therapies has significantly changed the treatment landscape. Therefore, identifying new molecular targets is essential for the development of more effective treatment strategies. In this study, we first accessed publicly available databases to obtain datasets and information related to MTAP . We then used lentiviral technology to knock down the MTAP gene and examined how this knockdown affects cell proliferation and migration using both in vitro and in vivo experimental approaches. MTAP deletion is commonly observed in various types of cancer. In lung cancer patients, MTAP deletion was associated with poor survival outcomes, with p values of 0.032 for squamous cell carcinoma and 0.039 for adenocarcinoma. In vitro experiments revealed that MTAP deletion enhanced the proliferation and migration of PC9 cells. Further in vivo studies demonstrated that MTAP knockdown was associated with an increased incidence of bone metastasis in mouse models. RNA sequencing analysis comparing MTAP -knockdown and parental PC9 cell lines revealed significant differences in gene expression. KEGG pathway analysis of the differentially expressed genes revealed enrichment in pathways related to signal transduction and the immune system. MTAP deletion is frequently observed across a wide range of cancers. In lung cancer patients, MTAP deletion is associated with poorer overall survival. Evidence from our study suggests that alterations in signal transduction and immune system pathways may play a role in the increased rate of bone metastasis observed in mouse models with MTAP deletion.