Abstract：
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.
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.
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.
摘要：
目的:探讨GMDS-AS1在肺腺癌(LUAD)上皮间质转化(EMT)中的作用。材料与方法：流式细胞术检测细胞功能，细胞计数试剂盒-8，伤口愈合测定和transwell测定。应用RNA免疫沉淀和下拉测定来确定GMDA-AS1、TAF15和SIRT1之间的相互作用。建立皮下异种移植模型。结果：GMDS-AS1下调与LUAD患者生存不良相关。GMDS-AS1抑制恶性表型，体外和体内肿瘤生长和EMT。机械上,GMDS-AS1招募TAF15蛋白以稳定SIRT1mRNA，从而脱乙酰p65并减少p65对MMP-9启动子的招募，从而抑制MMP-9的表达。结论:GMDS-AS1通过募集TAF15蛋白来抑制EMT，稳定SIRT1mRNA和去乙酰化p65，从而抑制LUAD的进展。
GMDS-AS1，一种新的lncRNA，与肺腺癌（LUAD）的进展有关，但GMDS-AS1调节LUAD进展的机制尚不清楚.这项研究发现，LUAD患者GMDS-AS1下调，其低表达与晚期转移和低生存率有关。GMDS-AS1的过表达显著损害肿瘤细胞的活力，扩散,迁移,侵袭和上皮间质转化，但细胞凋亡增强。此外,GMDS-AS1抑制小鼠肿瘤生长。GMDS-AS1通过募集TAF15蛋白稳定SIRT1mRNA并使p65脱乙酰而在LUAD中起肿瘤抑制因子的作用，从而减少了p65向MMP-9启动子的募集。这些发现揭示了LUAD进展的新机制，并提出了潜在的预后生物标志物和治疗靶标。
GMDS-AS1，一种新的lncRNA，与肺腺癌（LUAD）的进展有关，但GMDS-AS1调节LUAD进展的机制尚不清楚.这项研究发现，LUAD患者GMDS-AS1下调，其低表达与晚期转移和低生存率有关。GMDS-AS1的过表达显著损害肿瘤细胞的活力，扩散,迁移,侵袭和上皮间质转化，但细胞凋亡增强。此外,GMDS-AS1抑制小鼠肿瘤生长。GMDS-AS1通过募集TAF15蛋白稳定SIRT1mRNA并使p65脱乙酰而在LUAD中起肿瘤抑制因子的作用，从而减少了p65向MMP-9启动子的募集。这些发现揭示了LUAD进展的新机制，并提出了潜在的预后生物标志物和治疗靶标。
