Tazarotene-Induced Gene 3 (TIG3) Induces Apoptosis in Melanoma Cells Through the Modulation of Inhibitors of Apoptosis Proteins.

Background/Objectives: Retinoic acid has been shown to inhibit melanoma progression; however, its underlying mechanisms remain unclear. In this study, we investigated the role of the retinoic acid-inducible gene TIG3 in regulating melanoma cell growth, as well as elucidating its involvement in apoptosis. Methods: The expression of TIG3 in melanoma tissues was analyzed using a cDNA microarray. Cell viability and cell death were measured using the WST-1 and LDH assay kits, respectively. The gene expression changes that were induced by TIG3 were identified through RNA sequencing, while apoptosis-related pathways were examined using a human apoptosis protein array. The protein expression levels were further validated using Western blot analysis. Results: TIG3 expression was significantly downregulated in melanoma tissues. The overexpression of TIG3 in melanoma cells led to reduced cell viability and increased cell death. TIG3 suppressed the expression of several apoptosis-regulating proteins, including PON2, Fas, cIAP-1, Claspin, Clusterin, HTRA2, and Livin, while promoting the expression of cleaved Caspase-3. Supplementation with cIAP-1, HTRA2, or Livin partially reversed TIG3-induced Caspase-3 expression and cell death. Conclusions: Our findings suggest that TIG3 may contribute to the anti-melanoma effects of retinoic acid, with IAP family proteins playing a key role in the TIG3-mediated regulation of melanoma cell survival.