Fuente: Biomolecules - Revista científica (MDPI) Biomolecules, Vol. 15, Pages 1611: Modulation of Spliceosomal Proteins hnRNPH1 and H2 Increases Melanoma Cell Pro-Inflammatory Signaling In Vitro
Biomolecules doi: 10.3390/biom15111611
Authors:
Maab Sultan
Shuai Ma
Juan Diez
Sadeeshkumar Velayutham
Yousef Al-Harbi
Jun Yong Choi
Keiran S. M. Smalley
Lubov Nathanson
Vladimir Beljanski
Dmitriy Minond

Melanoma is the most aggressive and deadliest form of skin cancer, and the current treatments of melanoma have many limitations, which necessitate discovering new compounds and targets for melanoma. Two probes, 2155-14 and 2155-18, were identified to induce apoptotic cell death, autophagy, and immune signaling modulation through hnRNPH1/H2-dependent mechanisms. RNA sequencing following the siRNA-mediated knockdown of hnRNPH2 in melanoma cells revealed an enrichment of immune-related signaling pathways. The present study investigated the effect of genetic and pharmacologic downregulation of hnRNPH1/H2 on melanoma immunogenicity in vitro. Our results indicated that treating melanoma cell lines with 2155-14 and 2155-18 led to hnRNPH1/H2 downregulation, whereas hnRNPH2 siRNA treatment led to only hnRNPH2 downregulation. Both types of treatment resulted in a significant upregulation of pro-inflammatory pathways and simultaneous downregulation of anti-inflammatory pathways. These findings provide the first insight into the role of hnRNPH1/H2 as critical drivers of melanoma immunogenicity and suggest their potential as novel therapeutic targets for enhancing melanoma treatment outcomes. This study underscores the impact of post-transcriptional regulation on the immune environment in melanoma and in cancer in general.