Department of Dermatology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China.
Department of Radiotherapy, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231184842. doi: 10.1177/15330338231184842.
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. 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 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. 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. TUBB4A may be a prognostic biomarker and therapeutic target for melanoma.
黑色素瘤是具有高转移潜能的最恶性皮肤癌之一。越来越多的证据表明,β-微管蛋白 4A(TUBB4A)在几种人类癌症的发生和发展中起关键作用。然而,TUBB4A 在皮肤黑色素瘤中的潜在功能仍有待确定。
我们首先基于基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据集对皮肤黑色素瘤组织和正常组织进行了差异表达分析,然后进行了生存分析以确定与预后相关的关键基因。我们进一步进行了生化实验来验证关键基因 TUBB4A 的功能作用。我们使用两种 TUBB4A 的小分子抑制剂,双氢青蒿素(DHA)和诺考达唑,来验证 TUBB4A 对黑色素瘤细胞凋亡和细胞周期的影响。
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 共表达的基因富集在与黑色素瘤相关的途径和功能中。实验结果表明,TUBB4A 的敲低抑制了 A375 和 B16-F10 黑色素瘤细胞的增殖和迁移。此外,DHA 和诺考达唑促进了黑色素瘤细胞的凋亡,并阻断了黑色素瘤肿瘤细胞在 G2/M 期的周期。
TUBB4A 可能是黑色素瘤的预后生物标志物和治疗靶标。