Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma

Deregulation or loss of the human leukocyte antigen class I (HLA-I) molecules on tumor cells leading to inhibition of CD8+ T cell recognition is an important tumor immune escape strategy, which could be caused by a posttranscriptional control of molecules in the HLA-I pathway mediated by RNA-binding...

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Main Authors: Yuan Wang, Barbara Seliger
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:OncoImmunology
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Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2024.2370928
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author Yuan Wang
Barbara Seliger
author_facet Yuan Wang
Barbara Seliger
author_sort Yuan Wang
collection DOAJ
description Deregulation or loss of the human leukocyte antigen class I (HLA-I) molecules on tumor cells leading to inhibition of CD8+ T cell recognition is an important tumor immune escape strategy, which could be caused by a posttranscriptional control of molecules in the HLA-I pathway mediated by RNA-binding proteins (RBPs). So far, there exists only limited information about the interaction of RBPs with HLA-I-associated molecules, but own work demonstrated a binding of the heterogeneous ribonucleoprotein C (hnRNP C) to the 3’ untranslated region (UTR) of the TAP-associated glycoprotein tapasin (tpn). In this study, in silico analysis of pan-cancer TCGA datasets revealed that hnRNP C is higher expressed in tumor specimens compared to corresponding normal tissues, which is negatively correlated to tpn expression, T cell infiltration and the overall survival of tumor patients. Functional analysis demonstrated an upregulation of tpn expression upon siRNA-mediated downregulation of hnRNP C, which is accompanied by an increased HLA-I surface expression. Thus, hnRNP C has been identified to target tpn and its inhibition could improve the HLA-I surface expression on melanoma cells suggesting its use as a possible biomarker for T-cell-based tumor immunotherapies.
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spelling doaj-art-9cbec6a5f39444e69be06d5bacfdd2b22025-08-20T02:38:26ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2370928Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanomaYuan Wang0Barbara Seliger1Institute for Medical Immunology, Martin Luther University of Halle-Wittenberg, Halle (Saale), GermanyInstitute for Medical Immunology, Martin Luther University of Halle-Wittenberg, Halle (Saale), GermanyDeregulation or loss of the human leukocyte antigen class I (HLA-I) molecules on tumor cells leading to inhibition of CD8+ T cell recognition is an important tumor immune escape strategy, which could be caused by a posttranscriptional control of molecules in the HLA-I pathway mediated by RNA-binding proteins (RBPs). So far, there exists only limited information about the interaction of RBPs with HLA-I-associated molecules, but own work demonstrated a binding of the heterogeneous ribonucleoprotein C (hnRNP C) to the 3’ untranslated region (UTR) of the TAP-associated glycoprotein tapasin (tpn). In this study, in silico analysis of pan-cancer TCGA datasets revealed that hnRNP C is higher expressed in tumor specimens compared to corresponding normal tissues, which is negatively correlated to tpn expression, T cell infiltration and the overall survival of tumor patients. Functional analysis demonstrated an upregulation of tpn expression upon siRNA-mediated downregulation of hnRNP C, which is accompanied by an increased HLA-I surface expression. Thus, hnRNP C has been identified to target tpn and its inhibition could improve the HLA-I surface expression on melanoma cells suggesting its use as a possible biomarker for T-cell-based tumor immunotherapies.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2370928Antigen processing and presentationHNRNPCmelanomaRNA-binding proteintapasintumor immune evasion
spellingShingle Yuan Wang
Barbara Seliger
Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma
OncoImmunology
Antigen processing and presentation
HNRNPC
melanoma
RNA-binding protein
tapasin
tumor immune evasion
title Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma
title_full Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma
title_fullStr Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma
title_full_unstemmed Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma
title_short Identification of RNA-binding protein hnRNP C targeting the 3’UTR of the TAP-associated glycoprotein tapasin in melanoma
title_sort identification of rna binding protein hnrnp c targeting the 3 utr of the tap associated glycoprotein tapasin in melanoma
topic Antigen processing and presentation
HNRNPC
melanoma
RNA-binding protein
tapasin
tumor immune evasion
url https://www.tandfonline.com/doi/10.1080/2162402X.2024.2370928
work_keys_str_mv AT yuanwang identificationofrnabindingproteinhnrnpctargetingthe3utrofthetapassociatedglycoproteintapasininmelanoma
AT barbaraseliger identificationofrnabindingproteinhnrnpctargetingthe3utrofthetapassociatedglycoproteintapasininmelanoma