LncRNA DBH-AS1 facilitates the tumorigenesis of melanoma by targeting miR-233-3p via IGF-1R/Akt signaling

X.-X. Chen, N. Zhang, X.-F. Fu, Y. Jiang, M.-Y. Wang

Department of Dermatology, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China. Wangmeiyan600@sina.com

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• Oncology

OBJECTIVE: While Long Noncoding RNAs (LncRNAs) are well-known to modulate human cancer progression, the specific function of DBH-AS1 in melanoma remains to be fully established. The study will investigate the role of DBH-AS1 in melanoma cell.

PATIENTS AND METHODS: The expression profiles of DBH-AS1, miR-223-3p, and IGF-1R in melanoma tissues and cell lines were determined by RT-qPCR analysis. CCK-8 assay, colony assays and transwell assay were employed to analyze the effects of DBH-AS1 on the proliferation, migration, and invasion in GC cells. Bioinformatics analysis and Dual-Luciferase reporter assay determined the direct binding relation between DBH-AS1, miR-223-3p and IGF-1R in GC.

RESULTS: Herein, we observed significant reductions in DBH-AS1 expression in melanoma tumor tissues and cell lines. Knockdown DBH-AS1 in melanoma cells impaired their proliferative, migratory, and invasive potential. We determined that DBH-AS1 was able to modulate insulin growth factor receptor (IGF-1R) expression as a competing endogenous RNA for DBH-AS1. In line with this finding, the knockdown DBH-AS1 was associated with decreases in the expression of glucose transporter (GLUT)-1 and a consequent inhibition of glucose uptake, lactate production, and ATP generation by melanoma cells.

CONCLUSIONS: These findings therefore suggest that DBH-AS1 can enhance glycolytic activity in melanoma cells, thereby disrupting melanoma progression via miR-223-3p/EGFR/AKT axis. As such this signaling axis may be a viable therapeutic target for melanoma treatment in human patients.

 

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