{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:38:23Z","timestamp":1763390303870,"version":"3.45.0"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006827","name":"Florida Department of Health","doi-asserted-by":"publisher","award":["22B09"],"award-info":[{"award-number":["22B09"]}],"id":[{"id":"10.13039\/100006827","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIGMS\/NIH","award":["S10GM154296"],"award-info":[{"award-number":["S10GM154296"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biom15111611","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T14:04:07Z","timestamp":1763388247000},"page":"1611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Spliceosomal Proteins hnRNPH1 and H2 Increases Melanoma Cell Pro-Inflammatory Signaling In Vitro"],"prefix":"10.3390","volume":"15","author":[{"given":"Maab","family":"Sultan","sequence":"first","affiliation":[{"name":"Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Diez","sequence":"additional","affiliation":[{"name":"Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"},{"name":"Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321 College Avenue, CCR r.605, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0694-7612","authenticated-orcid":false,"given":"Sadeeshkumar","family":"Velayutham","sequence":"additional","affiliation":[{"name":"Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"},{"name":"Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321 College Avenue, CCR r.605, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4201-959X","authenticated-orcid":false,"given":"Yousef","family":"Al-Harbi","sequence":"additional","affiliation":[{"name":"Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"},{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah 52571, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-6440","authenticated-orcid":false,"given":"Jun Yong","family":"Choi","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA"},{"name":"Department of Chemistry and Biochemistry, Queens College, 65-30 Kissena Boulevard, Flushing, NY 11367, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiran S. M.","family":"Smalley","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-9083","authenticated-orcid":false,"given":"Lubov","family":"Nathanson","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-1628","authenticated-orcid":false,"given":"Vladimir","family":"Beljanski","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitriy","family":"Minond","sequence":"additional","affiliation":[{"name":"Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, 3321 College Avenue, Fort Lauderdale, FL 33314, USA"},{"name":"Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321 College Avenue, CCR r.605, Fort Lauderdale, FL 33314, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. 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