Although recent therapeutic advances based on our understanding of molecular phenomena have prolonged the survival of melanoma patients, the prognosis of melanoma remains dismal and further understanding of the underlying mechanism of melanoma progression is needed. In this study, differential expression analyses revealed that many genes, including AKT1 and CDK2, play important roles in melanoma. Functional analyses of differentially expressed genes (DEGs), obtained from the GEO (Gene Expression Omnibus) database, indicated that high proliferative and metastatic abilities are the main characteristics of melanoma and that the PI3K and MAPK pathways play essential roles in melanoma progression. Among these DEGs, major facilitator superfamily domain-containing 12 (MFSD12) was found to have significantly and specifically upregulated expression in melanoma, and elevated MFSD12 level promoted cell proliferation by promoting cell cycle progression. Mechanistically, MFSD12 upregulation was found to activate PI3K signaling, and a PI3K inhibitor reversed the increase in cell proliferation endowed by MFSD12 upregulation. Clinically, high MFSD12 expression was positively associated with shorter overall survival (OS) and disease-free survival (DFS) in melanoma patients, and MFSD12 was an independent prognostic factor for OS and DFS in melanoma patients. Therapeutically, in vivo assays further confirmed that MFSD12 interference inhibited tumor growth and lung metastasis in melanoma. In conclusion, elevated MFSD12 expression promotes melanoma cell proliferation, and MFSD12 is a valuable prognostic biomarker and promising therapeutic target in melanoma.

中文翻译：

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基于生物信息学的分析显示，MFSD12升高是细胞增殖的关键促进因素，也是黑色素瘤的潜在治疗靶标。

尽管基于我们对分子现象的理解，最近的治疗进展延长了黑色素瘤患者的生存期，但黑色素瘤的预后仍然令人沮丧，因此需要进一步了解黑色素瘤进展的潜在机制。在这项研究中，差异表达分析表明，包括AKT1和CDK2在内的许多基因在黑色素瘤中起重要作用。从GEO（Gene Expression Omnibus）数据库获得的差异表达基因（DEG）的功能分析表明，高增殖和转移能力是黑色素瘤的主要特征，而PI3K和MAPK途径在黑色素瘤的进展中起着至关重要的作用。在这些DEG中，发现主要的促进子超家族结构域含有12（MFSD12）在黑素瘤中有明显且特异上调的表达，而升高的MFSD12水平则通过促进细胞周期进程来促进细胞增殖。从机制上讲，发现MFSD12上调激活了PI3K信号传导，PI3​​K抑制剂逆转了MFSD12上调赋予的细胞增殖的增加。临床上，MFSD12的高表达与黑色素瘤患者较短的总生存期（OS）和无病生存期（DFS）正相关，MFSD12是黑色素瘤患者OS和DFS的独立预后因素。治疗上，体内测定进一步证实了MFSD12干扰抑制了黑色素瘤中的肿瘤生长和肺转移。总之，升高的MFSD12表达可促进黑色素瘤细胞增殖，