Identification of TUBB4A as a Prognostic Biomarker of Melanoma by Transcriptomic Data and in vitro Experiments

semanticscholar(2021)

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摘要
Background Melanoma is one of the most malignant skin carcinomas with high metastatic potential. Increasing evidences have demonstrated that β-tubulin 4A (TUBB4A) play key role in 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 differential expression analysis between skin melanoma tissues and normal tissues from GEO and TCGA datasets, and then ran survival analysis to identify prognostic-related key genes. We went further to conduct the verification of in vitro biochemical experiments to explore the functional roles of key gene TUBB4A. Two small molecule inhibitors of TUBB4A, Dihydroartemisinin (DHA) and Nocodazole, were used to examined the effect on apoptosis and cell cycle progression of melanoma cells. Results We found that TUBB4A is markedly correlated to the overall survival of cutaneous melanoma patients. The co-expressed genes with TUBB4A are enriched in the melanoma-related pathways and function. Then, the experimental results showed that knockdown of TUBB4A inhibit the proliferation and migration of A375 and B16-F10 melanoma cells. Moreover, two small molecular agents targeting TUBB4A, Dihydroartemisinin and Nonocodazole, dpromote the apoptosis of melanoma cells and made the tumor cells significantly blocked in G2/M stage. Conclusion We identified and validated in vitro that TUBB4A may be a prognostic biomarker and therapeutic target for melanoma.
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