Abstract

Melanoma is considered as the most frequent primary malignancy occurring in skin. Accumulating studies have suggested that long non-coding RNAs (lncRNAs) play critical parts in multiple cancers. In this study, we explored the molecular mechanism of ZBED3 antisense RNA 1 (ZBED3-AS1) in melanoma. We observed that ZBED3-AS1 expression was remarkably up-regulated in melanoma tissues, and high ZBED3-AS1 level was linked to unsatisfactory survival of melanoma patients. Then, we discovered that ZBED3-AS1 was overexpressed in melanoma cells compared with human epidermal melanocytes. In addition, loss-of-function assays verified that ZBED3-AS1 knockdown restrained cell proliferation, migration, epithelial-mesenchymal transition (EMT) and stemness in melanoma. In addition, signal transducer and activator of transcription 3 (STAT3), which also showed tumor-facilitating functions in melanoma, was confirmed as a transcriptional activator of ZBED3-AS1. Moreover, ZBED3-AS1 enhanced the expression of AT-rich interaction domain 4B (ARID4B) through sequestering miR-381-3p. Importantly, we further confirmed that ZBED3-AS1 promoted the malignant progression of melanoma by regulating miR-381-3p/ARID4B axis to activate the phosphatidylinositol 3-kinase/AKT serine/threonine kinase (PI3K/AKT) signaling pathway. In a word, our research might provide a novel therapeutic target for melanoma.

摘要

黑色素瘤被认为是皮肤中最常见的原发性恶性肿瘤。越来越多的研究表明，长链非编码 RNA (lncRNA) 在多种癌症中发挥着关键作用。在本研究中，我们探讨了 ZBED3 反义 RNA 1 (ZBED3-AS1) 在黑色素瘤中的分子机制。我们观察到 ZBED3-AS1 表达在黑色素瘤组织中显着上调，并且高 ZBED3-AS1 水平与黑色素瘤患者的不满意存活率有关。然后，我们发现与人类表皮黑色素细胞相比，ZBED3-AS1 在黑色素瘤细胞中过度表达。此外，功能丧失测定证实 ZBED3-AS1 敲低抑制了黑色素瘤中的细胞增殖、迁移、上皮-间质转化 (EMT) 和干性。此外，信号转导和转录激活因子 3 (STAT3)，在黑色素瘤中也显示出促进肿瘤的功能，被证实是 ZBED3-AS1 的转录激活剂。此外，ZBED3-AS1 通过隔离 miR-381-3p 增强了富含 AT 的相互作用域 4B (ARID4B) 的表达。重要的是，我们进一步证实 ZBED3-AS1 通过调节 miR-381-3p/ARID4B 轴激活磷脂酰肌醇 3-激酶/AKT 丝氨酸/苏氨酸激酶 (PI3K/AKT) 信号通路促进黑色素瘤的恶性进展。总之，我们的研究可能为黑色素瘤提供新的治疗靶点。我们进一步证实ZBED3-AS1通过调节miR-381-3p/ARID4B轴激活磷脂酰肌醇3-激酶/AKT丝氨酸/苏氨酸激酶(PI3K/AKT)信号通路促进黑色素瘤的恶性进展。总之，我们的研究可能为黑色素瘤提供新的治疗靶点。我们进一步证实ZBED3-AS1通过调节miR-381-3p/ARID4B轴激活磷脂酰肌醇3-激酶/AKT丝氨酸/苏氨酸激酶(PI3K/AKT)信号通路促进黑色素瘤的恶性进展。总之，我们的研究可能为黑色素瘤提供新的治疗靶点。