黑素瘤细胞外泌体来源的环状RNA circ_0084043对淋巴管内皮细胞的调控作用及机制研究OA

Objective To study the regulation and mechanism of melanoma cells exosome-derived circular RNA circ_0084043 on lymphatic endothelial cells(LECs).Methods 84 melanoma tissue samples and 60 normal skin tissue samples were collected from January 2022 to June 2024.Then the expression level of circ_0084043 and microlymphatic vessel density(mlVD)were detected.Human melanoma cell line A375 was cultured and infected with negative control(NC)shRNA lentivirus or circ_0084043 shRNA lentivirus.Cultivate LECs were divided into control group(no exosomes were added),NC shRNA exosome group(exosomes from melanoma cells infected with NC shRNA lentivirus were added),and circ_0084043 shRNA exosome group(exosomes from melanoma cells infected with circ_0084043 shRNA lentivirus were added).The proliferation(A450 value),number of migration,length of lymphatic vessels,and the expression levels of hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were measured.Results The expression level of circ_0084043 and mlVD value in melanoma tissues were higher than those in normal skin tissues(P＜0.05).The relative expression level of circ_0084043 in melanoma tissues was positively correlated with mlVD value(r=0.419,P＜0.05).The A450 value,migration number,lymphatic length,HIF-1α and VEGF expression levels of LECs in NC shRNA exosome group were higher than those in control group(P＜0.05).The A450 value,migration number,lymphatic length,HIF-1α and VEGF expression levels of LECs in circ_0084043 shRNA exosome group were lower than those in NC shRNA exosome group(P＜0.05).Conclusion circ_0084043 derived from exosomes of melanoma cells promotes the proliferation,migration and lymphangiogenesis of LECs,and the possible molecular mechanisms related to the above-mentioned promoting effects is the activation of HIF-1α/VEGF axis.