Background Circular RNAs play crucial roles in tumor occurrence and progression. This research aimed to explore the role and potential mechanism of hsa_circ_0013359 (circ_0013359) in melanoma. Methods The levels of circ_0013359, microRNA-136-5p (miR-136-5p), and member RAS oncogene family (RAB9A) in melanoma tissues and cells were detected using quantitative reverse transcriptase-polymerase chain reaction or western blot. Cell proliferation, apoptosis, cell cycle, cell migration, and invasion were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2- H -tetrazolium bromide assay, colony formation assay, flow cytometry, and transwell assay. Glycolysis was determined by detecting glucose consumption, lactate production, and extracellular acidification rate. The levels of hexokinase 2 and lactate dehydrogenase A were examined by western blot. The targeting relationship between miR-136-5p and circ_0013359 or RAB9A was confirmed by dual-luciferase reporter assay. Xenograft experiments were used to analyze tumor growth in vivo . Results Circ_0013359 and RAB9A levels were increased, while the miR-136-5p level was reduced in melanoma tissues and cells. Circ_0013359 knockdown inhibited proliferation, migration, invasion, and glycolysis and promoted apoptosis and cycle arrest in A875 and SK-MEL-1 cells. Circ_0013359 sponged miR-136-5p to regulate melanoma progression. In addition, miR-136-5p suppressed melanoma progression by targeting RAB9A. Besides, circ_0013359 silencing inhibited tumor growth in vivo . Conclusion Depletion of circ_0013359 hindered melanoma progression by regulating miR-136-5p/RAB9A axis.

中文翻译：

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Circ_0013359通过调节miR-136-5p / RAB9A轴促进黑色素瘤的致瘤性

背景环形RNA在肿瘤的发生和发展中起着至关重要的作用。本研究旨在探讨hsa_circ_0013359（circ_0013359）在黑色素瘤中的作用和潜在机制。方法采用定量逆转录聚合酶链反应或蛋白质印迹法检测黑素瘤组织和细胞中circ_0013359，microRNA-136-5p（miR-136-5p）和RAS癌基因家族成员（RAB9A）的水平。通过3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2-H-溴化四氮唑测定，菌落形成测定，流式细胞术评估细胞增殖，凋亡，细胞周期，细胞迁移和侵袭，以及transwell分析。通过检测葡萄糖的消耗，乳酸的产生和细胞外酸化率来确定糖酵解。通过蛋白质印迹检查己糖激酶2和乳酸脱氢酶A的水平。通过双荧光素酶报告基因分析证实了miR-136-5p与circ_0013359或RAB9A之间的靶向关系。异种移植实验用于分析体内肿瘤的生长。结果黑色素瘤组织和细胞中Circ_0013359和RAB9A水平升高，而miR-136-5p水平降低。Circ_0013359组合式抑制A875和SK-MEL-1细胞的增殖，迁移，侵袭和糖酵解，并促进细胞凋亡和周期停滞。Circ_0013359用海绵擦拭miR-136-5p，以调节黑色素瘤的进展。另外，miR-136-5p通过靶向RAB9A抑制黑素瘤的进展。此外，circ_0013359沉默可抑制体内肿瘤的生长。结论circ_0013359的耗竭可通过调节miR-136-5p / RAB9A轴来阻止黑色素瘤的进展。