Overexpression of PPM1G promotes cell metabolism and activates the NOTCH signaling pathway in lung adenocarcinoma.

Abstract

Background: Lung adenocarcinoma (LUAD) is one of the most malignant types of cancer with a high incidence. Protein phosphatase, Mg²⁺/Mn²⁺-dependent 1G (PPM1G) has recently been reported to promote cancer progression; however, its specific role in LUAD remains unknown. Therefore, in this study, we aimed to clarify the roles of PPM1G in LUAD and the related the regulatory mechanisms.

Methods: We analyzed the expression profile of PPM1G in the LUAD dataset obtained from The Cancer Genome Atlas (TCGA) database using the Gene Expression Profiling Interactive Analysis (GEPIA) online tool and R software. The functions of PPM1G in LUAD were investigated by in vivo and in vitro assays. Gene set enrichment analysis (GSEA) was conducted to determine the signaling pathways that could be regulated by PPM1G.

Results: PPM1G was found to be highly expressed in LUAD tumor tissues than in non-tumor tissues and was correlated with the pathological and clinical stages of the disease and patient survival. PPM1G overexpression promoted cell proliferation, metastasis and glycolysis, while PPM1G knockdown conferred the opposite effects. Moreover, PPM1G knockdown promoted cell apoptosis and caused cell cycle arrest at the G1 phase. In vivo, PPM1G knockdown inhibited tumorigenesis. We found that NOTCH signaling as a key pathway associated with PPMIG overexpression.

Conclusions: Our results revealed that high PPM1G expression acted as a prognostic factor in LUAD and promoted LUAD cell growth, metastasis, and glycolysis. Mechanistically, PPM1G activated the NOTCH pathway to promote these effects, indicating its potential as a novel therapeutic target for treating LUAD.