Identification of TUBB4A as a Prognostic Biomarker of Melanoma by Transcriptomic Data and In Vitro Experiments

Technol Cancer Res Treat. 2023 Jan-Dec:22:15330338231184842. doi: 10.1177/15330338231184842.

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.

Keywords: TUBB4A; differential expression; melanoma; prognostic biomarker; tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Humans
  • Melanoma, Cutaneous Malignant
  • Melanoma, Experimental*
  • Nocodazole
  • Prognosis
  • Skin Neoplasms* / genetics
  • Transcriptome
  • Tubulin* / genetics

Substances

  • artenimol
  • Biomarkers
  • Nocodazole
  • TUBB4A protein, human
  • Tubulin