1. Long non-coding RNA SLC2A1-AS1 induced by GLI3 promotes aerobic glycolysis and progression in esophageal squamous cell carcinoma by sponging miR-378a-3p to enhance Glut1 expression.
- Author
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Liu H, Zhang Q, Song Y, Hao Y, Cui Y, Zhang X, Zhang X, Qin Y, Zhu G, Wang F, Dang J, Ma S, Zhang Y, Guo W, Li S, Guan F, and Fan T
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation physiology, Disease Progression, Esophageal Neoplasms genetics, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma genetics, Esophageal Squamous Cell Carcinoma pathology, Female, Heterografts, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs genetics, Nerve Tissue Proteins genetics, Prognosis, Zinc Finger Protein Gli3 genetics, Esophageal Neoplasms metabolism, Esophageal Squamous Cell Carcinoma metabolism, Glucose Transporter Type 1 biosynthesis, Glycolysis genetics, MicroRNAs metabolism, Nerve Tissue Proteins metabolism, RNA, Long Noncoding metabolism, Zinc Finger Protein Gli3 metabolism
- Abstract
Background: Emerging evidence demonstrates that lncRNAs play pivotal roles in tumor energy metabolism; however, the detailed mechanisms of lncRNAs in the regulation of tumor glycolysis remain largely unknown., Methods: The expression of SLC2A1-AS1 was investigated by TCGA, GEO dataset and qRT-PCR. The binding of GLI3 to SLC2A1-AS1 promoter was detected by Luciferase Reporter Assay System and Ago2-RIP assay. FISH was performed to determine the localization of SLC2A1-AS1 in ESCC cells. Double Luciferase Report assay was used to investigate the interaction of miR-378a-3p with SLC2A1-AS1 and Glut1. Gain-of-function and Loss-of-function assay were performed to dissect the function of SLC2A1-AS1/miR-378a-3p/Glut1 axis in ESCC progression in vitro and in vivo., Results: We identified a novel lncRNA SLC2A1-AS1 in ESCC. SLC2A1-AS1 was frequently overexpressed in ESCC tissues and cells, and its overexpression was associated with TNM stage, lymph node metastasis and poor prognosis of ESCC patients. Importantly, GLI3 and SLC2A1-AS1 formed a regulatory feedback loop in ESCC cells. SLC2A1-AS1 promoted cell growth in vitro and in vivo, migration and invasion, and suppressed apoptosis, leading to EMT progression and increased glycolysis in ESCC cells. SLC2A1-AS1 functioned as ceRNA for sponging miR-378a-3p, resulting in Glut1 overexpression in ESCC cells. MiR-378a-3p inhibited cell proliferation and invasion as well as induced apoptosis, resulting in reduced glycolysis, which was partly reversed by SLC2A1-AS1 or Glut1 overexpression in ESCC cells., Conclusion: SLC2A1-AS1 plays important roles in ESCC development and progression by regulating glycolysis, and SLC2A1-AS1/miR-378a-3p/Glut1 regulatory axis may be a novel therapeutic target in terms of metabolic remodeling of ESCC patients., (© 2021. The Author(s).)
- Published
- 2021
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