Melanoma is characterized by high mortality and poor prognosis due to metastasis. AFF4 (AF4/FMR2 family member 4), as a scaffold protein, is a component of the super elongation complex (SEC), and is involved in the progression of tumors, e.g., leukemia, head and neck squamous cell carcinoma (HNSCC). However, few studies on AFF4 have focused on melanoma. Here, AFF4 expression levels and clinicopathological features were evaluated in melanoma tissue samples. Then, we performed cell proliferation, migration and invasion assays in A375 and A2058 cells lines in vitro to evaluate the role of AFF4 in melanoma. The effects of AFF4 knockdown in vivo were characterized via a xenograft mouse model. Finally, the correlation between c-Jun and AFF4 protein levels in melanoma was analyzed by rescue assay and immunohistochemistry (IHC). We found that AFF4 expression was upregulated in melanoma tumor tissues and that AFF4 protein expression was also closely related to the prognosis of patients with cutaneous melanoma. Moreover, AFF4 could promote the invasion and migration of melanoma cells by mediating epithelial to mesenchymal transition (EMT). AFF4 might regulate c-Jun activity to promote the invasion and migration of melanoma cells. Importantly, c-Jun was regulated by the AFF4 promoted melanoma tumorigenesis in vivo. Taken together, AFF4 may be a novel oncogene that promotes melanoma progression through regulation of c-Jun activity.

黑色素瘤的特点是死亡率高，由于转移而预后差。作为支架蛋白的AFF4（AF4 / FMR2家族成员4）是超伸长复合物（SEC）的一个组成部分，并参与肿瘤的发展，例如白血病，头颈鳞状细胞癌（HNSCC）。但是，关于AFF4的研究很少集中在黑色素瘤上。在这里，评估了黑色素瘤组织样本中的AFF4表达水平和临床病理特征。然后，我们在A375和A2058细胞系中进行了细胞增殖，迁移和侵袭实验，以评估AFF4在黑色素瘤中的作用。AFF4敲低的体内作用通过异种移植小鼠模型表征。最后，通过救援分析和免疫组化（IHC）分析了黑色素瘤中c-Jun和AFF4蛋白水平之间的相关性。我们发现黑色素瘤肿瘤组织中AFF4表达上调，并且AFF4蛋白表达也与皮肤黑色素瘤患者的预后密切相关。此外，AFF4可以通过介导上皮向间质转化（EMT）促进黑色素瘤细胞的侵袭和迁移。AFF4可能调节c-Jun活性以促进黑色素瘤细胞的侵袭和迁移。重要的是，c-Jun在体内被AFF4促进的黑色素瘤肿瘤发生调控。综上所述，AFF4可能是一种新型的癌基因，可通过调节c-Jun活性促进黑色素瘤的进展。