Abstract LB239: Downregulation of spliceosomal proteins hnRNPH1 and H2 in WM266-4 melanoma cells induces immune signaling

Abstract This study aims to determine the effect of hnRNPH1/H2 (H1/H2) downregulation on immune-related genes in vitro. Due to the molecular heterogeneity of melanoma, it is difficult to treat it, which necessitates new approaches. We discovered compounds that selectively kill melanoma cells by binding to spliceosomal proteins hnRNPH1/H2. RNAseq of melanoma cells treated with H1/H2 siRNA showed upregulation of immune pathways. To validate this effect of genomic modulation of H1/H2 on immune gene expression, we used NanoString method. We treated both WM266-4 cell line and melanocytes with H1/H2 siRNA and scrambled siRNA to knockdown our target gene. Then, RNA was extracted and analyzed by NanoString. Analysis data of melanoma cell line showed a significant difference between RNA samples treated with scrambled and the one treated with siRNA in upregulating immune-related genes. In contrast, data of melanocytes revealed no significant difference between scrambled and siRNA samples and did not show upregulation of these genes. This implies the specificity of this response to melanoma cells. In conclusion, we hypothesize that downregulation of spliceosomal proteins H1/H2 can upregulate immune-related genes, which in turn can improve melanoma patients’ survival. Consequently, H1/H2 can be targeted as a novel therapeutic approach. Citation Format: Maab Sultan, Juan Diez, Keiran S.M. Smalley, Vladimir Beljanski, Lubov Nathonson, Dmitriy Minond. Downregulation of spliceosomal proteins hnRNPH1 and H2 in WM266-4 melanoma cells induces immune signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB239.