Xi Guangmin, Zhang Caibo, Yu Cong, Wang Yiya, Fu Jinfeng, Qi Haining, Suda Kenichi, Wu Guoying
School of Life Sciences, Qilu Normal University, Jinan, China.
College of Life and Geographic Sciences, Kashi University, Kashi, China.
Transl Lung Cancer Res. 2025 Jul 31;14(7):2771-2787. doi: 10.21037/tlcr-2025-659. Epub 2025 Jul 28.
Lung adenocarcinoma (LUAD) is one of the most malignant types of cancer with a high incidence. Protein phosphatase, Mg/Mn-dependent 1G () 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 in LUAD and the related the regulatory mechanisms.
We analyzed the expression profile of 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 in LUAD were investigated by and assays. Gene set enrichment analysis (GSEA) was conducted to determine the signaling pathways that could be regulated by 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. , PPM1G knockdown inhibited tumorigenesis. We found that NOTCH signaling as a key pathway associated with PPMIG overexpression.
Our results revealed that high expression acted as a prognostic factor in LUAD and promoted LUAD cell growth, metastasis, and glycolysis. Mechanistically, activated the NOTCH pathway to promote these effects, indicating its potential as a novel therapeutic target for treating LUAD.
肺腺癌（LUAD）是最具侵袭性的癌症类型之一，发病率很高。最近有报道称，镁/锰依赖的蛋白磷酸酶1G（PPM1G）可促进癌症进展；然而，其在肺腺癌中的具体作用尚不清楚。因此，在本研究中，我们旨在阐明PPM1G在肺腺癌中的作用及其相关调控机制。
我们使用基因表达谱交互式分析（GEPIA）在线工具和R软件，分析了从癌症基因组图谱（TCGA）数据库获得的肺腺癌数据集中PPM1G的表达谱。通过CCK-8和Transwell实验研究PPM1G在肺腺癌中的功能。进行基因集富集分析（GSEA）以确定可能受PPM1G调控的信号通路。
发现PPM1G在肺腺癌肿瘤组织中的表达高于非肿瘤组织，并且与疾病的病理和临床分期以及患者生存率相关。PPM1G过表达促进细胞增殖、转移和糖酵解，而PPM1G敲低则产生相反的效果。此外，PPM1G敲低促进细胞凋亡并导致细胞周期停滞在G1期。总之，PPM1G敲低抑制肿瘤发生。我们发现NOTCH信号通路是与PPM1G过表达相关的关键通路。
我们的结果表明，高PPM1G表达是肺腺癌的一个预后因素，并促进肺腺癌细胞的生长、转移和糖酵解。从机制上讲，PPM1G激活NOTCH通路以促进这些作用，表明其作为治疗肺腺癌的新型治疗靶点的潜力。
