PDF(Pubmed)
Abstract：
Background: Melanoma is one of the most malignant skin carcinomas with high metastatic potential. Increasing evidence has demonstrated that β-tubulin 4A (TUBB4A) plays a key role in the development and progression of several types of human cancer. However, the potential function of TUBB4A in cutaneous melanoma remains to be determined. Methods: We first performed a differential expression analysis based on skin melanoma tissues and normal tissues from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets and then a survival analysis to identify prognostic-related key genes. We further conducted in vitro biochemical experiments to verify the functional roles of the key gene TUBB4A. Two small-molecule inhibitors of TUBB4A, Dihydroartemisinin (DHA) and Nocodazole, were used to validate the effect of TUBB4A on the apoptosis and cell cycle of melanoma cells. Results: We found that TUBB4A expression was positively correlated to the overall survival (OS) of cutaneous melanoma patients. The coexpressed genes with TUBB4A were enriched in melanoma-related pathways and functions. The experimental results showed that knockdown of TUBB4A inhibited the proliferation and migration of A375 and B16-F10 melanoma cells. Moreover, DHA and Nocodazole promoted the apoptosis of melanoma cells and blocked the melanoma tumor cell cycle in the G2/M stage. Conclusion: TUBB4A may be a prognostic biomarker and therapeutic target for melanoma.
摘要：
背景：黑色素瘤是恶性程度最高的皮肤癌之一，具有很高的转移潜力。越来越多的证据表明，β-微管蛋白4A（TUBB4A）在几种类型的人类癌症的发生和发展中起着关键作用。然而,TUBB4A在皮肤黑色素瘤中的潜在功能仍有待确定。方法：我们首先基于来自基因表达综合（GEO）和癌症基因组图谱（TCGA）数据集的皮肤黑色素瘤组织和正常组织进行差异表达分析，然后进行生存分析以鉴定与预后相关的关键基因。我们进一步进行了体外生化实验，以验证关键基因TUBB4A的功能作用。两种小分子TUBB4A抑制剂，双氢青蒿素（DHA）和诺考达唑，用于验证TUBB4A对黑色素瘤细胞凋亡和细胞周期的影响。结果：我们发现TUBB4A的表达与皮肤黑色素瘤患者的总生存期（OS）呈正相关。与TUBB4A共表达的基因在黑色素瘤相关的途径和功能中富集。实验结果表明，敲低TUBB4A抑制A375和B16-F10黑色素瘤细胞的增殖和迁移。此外，DHA和Nocodazole在G2/M期促进黑色素瘤细胞凋亡并阻断黑色素瘤细胞周期。结论：TUBB4A可能是黑色素瘤的预后标志物和治疗靶点。
