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.

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.

• Authors: Hongtao Liu, Qing Zhang, Yinsen Song, Yibin Hao, Yunxia Cui, Xin Zhang, Xueying Zhang, Yue Qin, Guangzhao Zhu, Feng Wang, Jinghan Dang, Shanshan Ma, Yanting Zhang, Wenna Guo, Shenglei Li, Fangxia Guan, Tianli Fan
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 40 Issue 1 Pg. 287 (Sep 13 2021) ISSN: 1756-9966 [Electronic] England
• PMID: 34517880 (Publication Type: Journal Article, Retracted Publication)
• Copyright: © 2021. The Author(s).

Chemical References

• GLI3 protein, human
• Glucose Transporter Type 1
• MIRN378 microRNA, human
• MicroRNAs
• Nerve Tissue Proteins
• RNA, Long Noncoding
• SLC2A1 protein, human
• Zinc Finger Protein Gli3

Topics

• Animals
• Cell Line, Tumor
• Cell Proliferation (physiology)
• Disease Progression
• Esophageal Neoplasms (genetics, metabolism, pathology)
• Esophageal Squamous Cell Carcinoma (genetics, metabolism, pathology)
• Female
• Glucose Transporter Type 1 (biosynthesis)
• Glycolysis (genetics)
• Heterografts
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Prognosis
• RNA, Long Noncoding (metabolism)
• Zinc Finger Protein Gli3 (genetics, metabolism)