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Glutathiones' life in multi-cancers: especially their potential micropetides in liver hepatocellular carcinoma
Didi Ma1, Zhenguo Wu1, Mengying Zhang1
1Anhui Province Key Laboratory of Non-Coding RNA Basic and Clinical Transformation (Wannan Medical College), Central Laboratory, Yijishan Hospital of Wannan Medical College, Wuhu, 241000, China.
Background:
Glutathione plays critical roles in detoxifying xenobiotics, cell signaling, cell death and the antioxidant defence in an emerging body of evidence, the most abundant intracellular low molecular weight thiol in tissues. However, all glutathione metabolism pertinent genes (GMPGs) expression and their diagnostic/prognostic/micropeptide potential analyses have not been investigated to perform in pan-cancers.
Methods:
We gained GMPGs from the MsigDB 7.2, 12,123 samples were used to reveal the differentially expressed genes (DEGs) and the survival analysis in 32 types of cancers from TCGA, GTEx, and GEO datasets for the first time. All statistical analyses were performed by R for bioinformatics, such as DEGs, prognostic, diagnostic analysis, ceRNA, micropeptide prediction and immune infiltration. In addition, we utilized siRNA technology to target knockdown the expression of the G6PD gene in Huh7 hepatocellular carcinoma cells.
Results:
G6PD was significantly expressed and poor prognosis in liver hepatocellular carcinoma (LIHC) and predicted RBM26-AS1 encoded micropeptide might target G6PD in LIHC. In vitro experiments show that G6PD knockout in Huh7 cells reduces their proliferation, migration, and invasion capabilities.
Conclusions:
We confirmed that G6PD played a crucial role in the occurrence and progression of LIHC. G6PD is positively associated with Th2 cells in LIHC, regulating immune responses in the immune system. We considered that micropeptide RBM26-AS1 might be a new player involved in LIHC by interacting with G6PD, might perform a key function in liver cancer.
Insights
Glucose-6-phosphate dehydrogenase (G6PD) is crucial in liver cancer progression. This study reveals G6PD
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Glutathione is vital for cellular defense and detoxification.
- Glutathione metabolism pertinent genes (GMPGs) roles across cancers are understudied.
- Investigating GMPGs offers potential for cancer diagnostics and therapeutics.
Purpose of the Study:
- To analyze the expression and prognostic value of GMPGs in pan-cancers.
- To explore the diagnostic and therapeutic potential of GMPGs, including micropeptides.
- To investigate the role of G6PD in liver hepatocellular carcinoma (LIHC).
Main Methods:
- Utilized bioinformatics analysis on TCGA, GTEx, and GEO datasets (12,123 samples).
- Performed differential gene expression, survival, ceRNA, and micropeptide prediction analyses.
- Employed siRNA to knockdown G6PD expression in Huh7 hepatocellular carcinoma cells.
Main Results:
- G6PD showed significant expression and poor prognosis in LIHC.
- RBM26-AS1 was predicted to target G6PD, potentially acting as a micropeptide in LIHC.
- G6PD knockdown in vitro reduced LIHC cell proliferation, migration, and invasion.
Conclusions:
- G6PD plays a critical role in LIHC development and progression.
- G6PD is associated with Th2 cells, influencing immune responses in LIHC.
- Micropeptide RBM26-AS1 may interact with G6PD, contributing to liver cancer pathogenesis.
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