LncRNA FAM83H-AS1 promotes aerobic glycolysis and tumor progression by regulating miR-4684-5p/ZBTB38 axis in esophageal squamous cell carcinoma

Abstract Background: Dysregulation of lncRNAs is implicated in esophageal squamous cell carcinoma (ESCC) progression; However, the precise function of lncRNA FAM83H-AS1 in ESCC remains unknown. Methods: FAM83H-AS1, miR-4684-5p and ZBTB38 mRNA expressions were detected via qRT-PCR. ZBTB38, GLUT1 and LDH-A protein expressions were tested via Western blot. Cell proliferation, migration and invasion were evaluated via CCK-8 and transwell assay, respectively. A nude mouse xenograft model was used to investigate the role of FAM83H-AS1 in xenograft ESCC growth. The metabolic shift in ESCC cells was examined via glycolysis analysis. The interaction between FAM83H-AS1, miR-4684-5p and ZBTB38 was analyzed via computational algorithms, RNA pull-down, RIP and dual luciferase reporter assay. Results: We found that FAM83H-AS1 was upmodulated in ESCC cell lines. FAM83H-AS1 knockdown hampered ESCC cell proliferation, migration, invasion and aerobic glycolysis, while FAM83H-AS1 overexpression demonstrated the opposite effects. FAM83H-AS1 knockdown also delayed the tumor growth in vivo. Moreover, FAM83H-AS1 interacted with miR-4684-5p/ZBTB38 axis in ESCC cells. ZBTB38 overexpression or miR-4684-5p inhibition partially reversed the inhibitory effect of FAM83H-AS1 knockdown on cell migration, invasion and aerobic glycolysis in ESCC cells. Conclusion: Our present results indicate FAM83H-AS1 accelerated aerobic glycolysis and tumorigenesis of ESCC by sponging miR-4684-5p and triggering the expression of ZBTB38, providing new insights into mechanism of ESCC progression and therapeutic strategy.