GMFG (glia maturation factor gamma) inhibits lung cancer growth by activating p53 signaling pathway

Abstract

The tumor-promoting or tumor-suppressing functions of Glia maturation factor gamma (GMFG) were described in several cancers. However, how GMFG regulates lung cancer progression is elusive. Bioinformatics analysis was employed to analyze GMFG expression in lung adenocarcinoma (LUAD) and lung squamous cancer (LUSC) as well as its significance in prognosis prediction and diagnosis in lung cancer patients. CCK8 and colony formation assays were adopted to evaluate the impact of GMFG overexpressing and depleting on lung cancer cell proliferation. And in vivo experiments were implemented. Luciferase reporter assays were used to disclose the signaling pathway mediated by GMFG in lung cancer. GMFG expression was lower in LUSC and LUAD tissues compared with normal lung tissues based on TCGA and GTEx databases. Low GMFG expression was associated with lower overall survival and shorter disease specific survival compared high GMFG expression. In vitro loss and gain functions assays demonstrated that ectopically GMFG expression dampened the lung cancer cell proliferation while GMFG knockout escalated the cell proliferation. The promoting effect of GMFG knockout on lung cancer tumorgenesis was also observed in vivo. More interesting, GMFG overexpression reinforced the p53 signaling pathway in lung cancer cells, conversely GMFG deficiency disrupted p53 signaling pathway. In conclusion, we revealed that GMFG is fundamental to p53 signaling pathway to inhibit lung cancer progression, highlighting the importance of GMFG as a p53 inducer for lung cancer patient’s diagnosis and therapy.

Identification of GMFG as a novel biomarker in IgA nephropathy based on comprehensive bioinformatics analysis

“…Several studies have contributed to our understanding of GMFG's role in cancer. For instance, it has been shown to inhibit the growth of lung cancer by activating the p53 signaling pathway [ 50 ]. In the case of LGG, which exhibit higher levels of GMFG expression, it has been associated with worse overall survival [ 40 ].…”

Comprehensive analysis of co-expressed genes with TDP-43: prognostic and therapeutic potential in lung adenocarcinoma

“…Consequently, PRR11 represents a potential therapeutic target for lung cancer treatment. GMFG , a gene located on chromosome 19q13.2, comprises seven exons (Tang et al 2022 ). It belongs to the actin depolymerizing factor (ADF)/cofilin family, which is crucial in remodeling the actin cytoskeleton (Tang et al 2022 ).…”

“…GMFG , a gene located on chromosome 19q13.2, comprises seven exons (Tang et al 2022 ). It belongs to the actin depolymerizing factor (ADF)/cofilin family, which is crucial in remodeling the actin cytoskeleton (Tang et al 2022 ). A previous study suggests that GMFG expression is downregulated in LUAD tissues compared to normal lung tissues and that it may exert anti-cancer effects by activating the p53 signaling pathway, thereby inhibiting the progression of lung cancer (Tang et al 2022 ).…”

“…It belongs to the actin depolymerizing factor (ADF)/cofilin family, which is crucial in remodeling the actin cytoskeleton (Tang et al 2022 ). A previous study suggests that GMFG expression is downregulated in LUAD tissues compared to normal lung tissues and that it may exert anti-cancer effects by activating the p53 signaling pathway, thereby inhibiting the progression of lung cancer (Tang et al 2022 ). Furthermore, GMFG has been implicated in immune responses across various cancer types, exhibiting a positive association with immune regulation (Lan et al 2021 ).…”

In search of the ratio of miRNA expression as robust biomarkers for constructing stable diagnostic models among multi-center data

“…The performance verification data of the model are shown in Table 4. The five miRNAs of the three ERRmiR markers were significantly enriched in the p53 signaling, cell cycle, and PI3K-Akt pathways, which are widely reported to be associated with LUAD (Huang et al, 2022;Tang et al, 2022;Zhang et al, 2022) (Figure 6D).…”