%0 Journal Article
%T lncRNA GMDS-AS1 restrains lung adenocarcinoma progression via recruiting TAF15 protein to stabilize SIRT1 mRNA.
%A Peng W
%A Jiang J
%A Fu J
%A Duan H
%A Wang J
%A Duan C
%J Epigenomics
%V 15
%N 7
%D 2023 04 13
%M 37309595
%F 4.357
%R 10.2217/epi-2022-0432
%X Aim: To explore the roles of GMDS-AS1 in the epithelial-mesenchymal transition (EMT) of lung adenocarcinoma (LUAD). Materials & methods: Cell functions were detected by flow cytometry, cell counting kit-8, wound healing assays and transwell assays. RNA immunoprecipitation and pull-down assays were applied for determining the interaction among GMDA-AS1, TAF15 and SIRT1. A subcutaneous xenograft model was established. Results: GMDS-AS1 downregulation was associated with poor survival of LUAD patients. GMDS-AS1 repressed malignant phenotypes, tumor growth and EMT in vitro and in vivo. Mechanically, GMDS-AS1 recruited TAF15 protein to stabilize SIRT1 mRNA and thereby deacetylated p65 and reduced the recruitment of p65 to MMP-9 promoter, thus inhibiting MMP-9 expression. Conclusion: GMDS-AS1 represses EMT by recruiting TAF15 protein to stabilize SIRT1 mRNA and deacetylate p65, thus restraining LUAD progression.<BR>GMDS-AS1, a novel lncRNA, is involved in the progression of lung adenocarcinoma (LUAD), but the mechanism by which GMDS-AS1 regulates LUAD progression remains largely unknown. This study found that GMDS-AS1 was downregulated in LUAD patients, and its low expression was associated with advanced metastasis and poor survival. Overexpression of GMDS-AS1 significantly impaired tumor cell viability, proliferation, migration, invasion and epithelial–mesenchymal transition but enhanced apoptosis. In addition, GMDS-AS1 repressed tumor growth in mice. GMDS-AS1 functioned as a tumor suppressor in LUAD by recruiting TAF15 protein to stabilize SIRT1 mRNA and deacetylate p65, thus decreasing the recruitment of p65 to MMP-9 promoter. These findings have uncovered a novel mechanism underlying LUAD progression and suggested potential prognostic biomarkers and therapeutic targets.