Abstract
BackgroundCircular 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.MethodsThe 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.ResultsCirc_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.ConclusionDepletion of circ_0013359 hindered melanoma progression by regulating miR-136-5p/RAB9A axis.
Highlights
Melanoma is an aggressive skin cancer and the leading cause of skin cancer-related death [1]
We explored the interaction between circ_0013359 and miR-136-5p/member RAS oncogene family (RAB9A) axis in melanoma, which may provide new therapeutic targets for melanoma
The results suggested that the circ_0013359 level was markedly elevated in melanoma tissues compared to normal tissues (Figure 1b)
Summary
Melanoma is an aggressive skin cancer and the leading cause of skin cancer-related death [1]. The incidence of melanoma has increased year by year, while metastasis is still a serious obstacle to melanoma treatment [2,3]. Melanoma originates from melanocytes, accounting for only 5% of all skin cancers [4]. The 5-year survival rate of metastatic melanoma patients is only 5% [5]. Human adipose-derived mesenchymal stem cells expressing IP-10 could reduce melanoma tumor growth and lung metastasis [6]. Further understanding of melanoma’s underlying mechanisms is urgently needed to improve the poor prognosis of melanoma
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