MX2 protein is a dynamin-like GTPase2 that has recently been identified as an interferon-induced restriction factor of HIV-1 and other primate lentiviruses. A single nucleotide polymorphism (SNP), rs45430, in an intron of the MX2 gene, was previously reported as a novel melanoma susceptibility locus in genome-wide association studies. Functionally, however, it is still unclear whether and how MX2 contributes to melanoma susceptibility and tumorigenesis. Here, we show that MX2 is differentially expressed in melanoma tumors and cell lines, with most metastatic cell lines showing lower MX2 expression than primary melanoma cell lines and melanocytes. Furthermore, high expression of MX2 RNA in primary melanoma tumors is associated with better patient survival. Overexpression of MX2 reduces in vivo proliferation partially through inhibition of AKT activation, suggesting that it can act as a tumor suppressor in melanoma. However, we have also identified a subset of melanoma cell lines with high endogenous MX2 expression where downregulation of MX2 leads to reduced proliferation. In these cells, MX2 downregulation interfered with DNA replication and cell cycle processes. Collectively, our data for the first time show that MX2 is functionally involved in the regulation of melanoma proliferation but that its function is context-dependent.

中文翻译：

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MX 2 是黑色素瘤细胞中细胞周期的新型调节剂。

MX2 蛋白是一种动力蛋白样 GTPase2，最近被鉴定为干扰素诱导的 HIV-1 和其他灵长类慢病毒的限制因子。MX2 基因内含子中的单核苷酸多态性 (SNP) rs45430 先前被报道为全基因组关联研究中的新型黑色素瘤易感位点。然而，在功能上，尚不清楚 MX2 是否以及如何促进黑色素瘤易感性和肿瘤发生。在这里，我们显示 MX2 在黑色素瘤肿瘤和细胞系中差异表达，大多数转移性细胞系的 MX2 表达低于原代黑色素瘤细胞系和黑色素细胞。此外，MX2 RNA 在原发性黑色素瘤肿瘤中的高表达与更好的患者存活率相关。MX2 的过度表达通过抑制 AKT 激活部分减少体内增殖，表明它可以作为黑色素瘤的肿瘤抑制因子。然而，我们还鉴定了具有高内源性 MX2 表达的黑色素瘤细胞系的子集，其中 MX2 的下调导致增殖减少。在这些细胞中，MX2 下调干扰了 DNA 复制和细胞周期过程。总的来说，我们的数据首次表明 MX2 在功能上参与黑色素瘤增殖的调节，但其功能是依赖于环境的。MX2 下调干扰 DNA 复制和细胞周期过程。总的来说，我们的数据首次表明 MX2 在功能上参与黑色素瘤增殖的调节，但其功能是依赖于环境的。MX2 下调干扰 DNA 复制和细胞周期过程。总的来说，我们的数据首次表明 MX2 在功能上参与黑色素瘤增殖的调节，但其功能是依赖于环境的。