Glycoprotein M6A Suppresses Lung Adenocarcinoma Progression via Inhibition of the PI3K/AKT Pathway.

Abstract

Lung adenocarcinoma is the most common subtype of lung cancer and has high morbidity and mortality. Glycoprotein M6A (GPM6A) is a neuronal membrane glycoprotein reported to be related with cancer. However, studies on GPM6A in lung adenocarcinoma are rare. This study aimed to investigate the role of GPM6A in lung adenocarcinoma and its potential mechanism. GPM6A mRNA expression was analysed in 33 types of cancers using The Cancer Genome Atlas (TCGA) datasets. It was compared among normal lung tissues, lung adenocarcinoma tissues, and adjacent tissues using the Oncomine database. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to detect GPM6A expression in human lung adenocarcinoma cell lines (A549 and H1299) and normal pulmonary epithelial cells (BEAS-2B). When GPM6A was inhibited, cell proliferative capacity was detected by Cell Counting Kit 8 (CCK8), EdU, and colony formation assays. Cell migration ability was detected by wound healing and transwell assays. The expression of epithelial-mesenchymal transition (EMT) markers was detected by Western blotting (WB) and RT-qPCR. When GPM6A was overexpressed, cell proliferation and migration were detected again. Ten nude mice were subcutaneously injected with cells overexpressing GPM6A or empty vector, and the tumor size was recorded on day 14 and then measured every 3 days thereafter. The final tumor weight was measured on day 36. Furthermore, the expressions of phosphoinositide 3-kinase (PI3K), phosphorylated PI3K, AKT, and phosphorylated AKT were detected by WB. Results showed that GPM6A mRNA expression decreased in 15 types of tumors in TCGA dataset. GPM6A expression was lower in lung adenocarcinoma than in normal lung tissues or adjacent tissues in the Oncomine dataset. Similar results were found in lung adenocarcinoma cells. The function study showed that GPM6A downregulation enhanced the proliferation, migration, and EMT of lung adenocarcinoma cells, while GPM6A upregulation inhibited their development. The xenograft results suggested that GPM6A upregulation delayed tumor growth and reduced tumor weight. Moreover, WB showed that GPM6A knockdown activated the PI3K/AKT pathway, while GPM6A upregulation inhibited the activation of the PI3K/AKT pathway. In conclusion, GPM6A suppresses lung adenocarcinoma progression via inhibition of the PI3K/AKT pathway. Thus, GPM6A could be a possible treatment target for lung cancer therapy.