Comprehensive Investigation into the Role of Ubiquitin-Conjugating Enzyme E2S in Melanoma Development

Ubiquitin-conjugating enzyme E2S (UBE2S) is involved in protein degradation and signal transduction, but its function in the development of melanoma is unclear. We focused on the role of UBE2S in melanoma development both in vitro and in vivo. UBE2S was overexpressed in malignant melanoma cells and tissues, and UBE2S expression was significantly different between tumor node metastasis staging T4 and T1/T2/T3. We designed UBE2S short hairpin RNA (shUBE2S) and transfected it into A375, SK-MEL-28, and MUM-2B cells using lentivirus. By whole-genome filtering, 247 genes and 265 genes were upregulated and downregulated, respectively, in shUBE2S-treated melanoma; these genes were mainly involved in immune reactions, apoptosis, DNA damage repair, and cell movement. The proliferation of melanoma cells was inhibited, apoptosis was increased, and cell cycle was arrested in G1/S in shUBE2S-treated melanoma. Expression of epithelial to mesenchymal transition-related proteins was significantly suppressed, and tumor growth was also suppressed in shUBE2S BALB/C nude mice. shUBE2S treatment may cause cell cycle arrest in G1/S phase, inhibit proliferation, induce apoptosis, and suppress tumor growth through DNA damage repair, epithelial to mesenchymal transition inhibition, protein kinase B-mTOR pathway, NF-kappa B signaling, and immune reactions, which provides a comprehensive understanding of the role of UBE2S in melanoma development and the need for advanced clinical research into UBE2S.