Circ_0016418 promotes melanoma development and glutamine catabolism by regulating the miR-605-5p/GLS axis

Background: Malignant melanoma is a skin cancer with a high rate of metastasis. Numerous circular RNAs (circRNAs) have been shown to play vital roles in melanoma. This research aimed to investigate the role and molecular basis of circ_0016418 in melanoma progression.

Methods: The abundanced of circ_0016418, miR-605-5p and glutaminase (GLS) were measured using quantitative real-time polymerase chain reaction or western blot analysis. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell migration and invasion were assessed by transwell assay. Cell cycle and apoptosis were monitored by flow cytometry. The levels of glutamine consumption and glutamate were examined using commercial kits. The interaction among circ_0016418, miR-605-5p and GLS was verified with the dual-luciferase reporter assay. A xenograft model was used to analyze tumor growth in vivo.

Results: Circ_0016418 and GLS were up-regulated, while miR-605-5p was down-regulated in melanoma tissues and cells. Circ_0016418 silencing hindered cell proliferation, metastasis, and glutamine catabolism and promoted cell cycle arrest and apoptosis in A375 and A875 cells. Circ_0016418 modulated melanoma progression and glutamine catabolism through sponging miR-605-5p. Also, miR-605-5p inhibited melanoma progression and glutamine catabolism by targeting GLS. Moreover, circ_0016418 depletion blocked tumor growth in vivo.

Conclusion: Knockdown of circ_0016418 suppressed melanoma development and glutamine catabolism by modulating the miR-605-5p/GLS pathway.