ABSTRACT
OBJECTIVES: To determine the expression and function of glutamate-cysteine ligase catalytic (GCLC) and glutamate-cysteine ligase catalytic modifier (GCLM) in gastric adenocarcinoma. METHODS: Bioinformatics was used to analyze the expression of GCLC and GCLM. We download and analyzed the expression of gastric adenocarcinoma patients from TCGA database. Moreover, the method of immunochemistry was used to verify the expression of GCLC and GCLM in gastric adenocarcinoma. RESULTS: At first, the expression of GCLC and GCLM in gastric adenocarcinoma tissues were both significantly higher compared with normal tissues analyzed via TCGA database. Then, gastric adenocarcinoma tissues were collected and performed with immunochemistry. The gastric adenocarcinoma with positive staining for GCLC and GCLM was 77% and 80%, respectively, which was significantly higher compared with adjacent normal tissues (9% and 11%, respectively). CONCLUSIONS: The disordered expression of GCLC and GCLM in gastric adenocarcinoma suggested that these factors may induce tumorigenesis and may be a novel target for diagnosis and treatment of gastric adenocarcinoma.
Subject(s)
Adenocarcinoma , Glutamate-Cysteine Ligase , Stomach Neoplasms , Humans , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Glutamate-Cysteine Ligase/genetics , Glutamate-Cysteine Ligase/metabolism , Glutathione , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolismABSTRACT
Non-small cell lung cancer (NSCLC) is one of the most malignant epithelial tumors. Studies have suggested that DNA hypermethylation of promoters and abnormal histone modifications could induce tumor suppressor genes (TSGs) downregulation in NSCLC. However, the exact mechanism of TSGs downregulation remains unclear. In this study, we found that there is no difference in the regions of most TSGs promoters in NSCLC. Moreover, we found that there is no DNA methylation difference in the region of VILL promoter in NSCLC compared with adjacent tissue samples by pyrosequencing. We further demonstrated that VILL was markedly reactivated in A549 and H1703 cells infected with miR-26A1 lentivirus while this activation was inhibited by JQ1, an enhancer inhibitor. In addition, we identified that miR-26A1 could function as a tumor suppressor to inhibit proliferation and metastasis of NSCLC cells. Chromatin immunoprecipitation assays revealed that overexpression of miR-26A1 could significantly induce the enrichment of H3K27ac at the enhancer regions in A549 cells. To sum up, our findings revealed that enhancer-mediated TSGs regulation occured in NSCLC, suggesting that miR-26A1 could serve as a key regulator and may be a potential therapeutic target for NSCLC.
