RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma
Hu Antigen R, also known as ELAVL1 (HuR), is a key posttranscriptional regulator in eukaryotic cells. HuR overexpression promotes several malignancies, including head and neck squamous cell carcinoma (HNSCC). However, its immune dysfunction-associated tumorigenesis pathways remain unknown. We examin...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Oral Oncology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772906024001420 |
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| author | Mrinmoyee Majumder Harinarayanan Janakiraman Paramita Chakraborty Anitha Vijayakumar Sari Mayhue Hong Yu Toros Dincman Romeo Martin Elizabeth O'Quinn Shikhar Mehrotra Viswanathan Palanisamy |
| author_facet | Mrinmoyee Majumder Harinarayanan Janakiraman Paramita Chakraborty Anitha Vijayakumar Sari Mayhue Hong Yu Toros Dincman Romeo Martin Elizabeth O'Quinn Shikhar Mehrotra Viswanathan Palanisamy |
| author_sort | Mrinmoyee Majumder |
| collection | DOAJ |
| description | Hu Antigen R, also known as ELAVL1 (HuR), is a key posttranscriptional regulator in eukaryotic cells. HuR overexpression promotes several malignancies, including head and neck squamous cell carcinoma (HNSCC). However, its immune dysfunction-associated tumorigenesis pathways remain unknown. We examined HuR's effects on oral malignancies and immune cell function in vitro and in vivo using oral carcinoma cells and transgenic HuR knockout (KO) mice. CRISPR/Cas9-mediated HuR deletion in mice syngeneic oral cancer cells eliminated colony formation and tumor development. HuR-KO tumors had a lower tumor volume, fewer CD4+CD25+FoxP3+ regulatory T cells, and more CD8+ T cells, suggesting that HuR may suppress the immune response during oral cancer progression. In contrast, HuR KO oral epithelial tissues are resistant to 4NQO-induced oral malignancies compared to control tumor-bearing mice. HuR KO mice showed fewer Tregs and greater IFN levels than WT tumor-bearing mice, suggesting anticancer activity. Finally, the HuR inhibitor pyrvinium pamoate lowers tumor burden by enhancing CD8+ infiltration at the expense of CD4+, suggesting anticancer benefits. Thus, HuR-dependent oral neoplasia relies on immunological dysfunction, suggesting that decreasing HuR may boost antitumor potential and offer a novel HNSCC therapy. |
| format | Article |
| id | doaj-art-29940c3c40ad44ef86192a148ce6518f |
| institution | Kabale University |
| issn | 2772-9060 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Oral Oncology Reports |
| spelling | doaj-art-29940c3c40ad44ef86192a148ce6518f2025-01-09T06:15:43ZengElsevierOral Oncology Reports2772-90602024-06-0110100296RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinomaMrinmoyee Majumder0Harinarayanan Janakiraman1Paramita Chakraborty2Anitha Vijayakumar3Sari Mayhue4Hong Yu5Toros Dincman6Romeo Martin7Elizabeth O'Quinn8Shikhar Mehrotra9Viswanathan Palanisamy10Department of Biochemistry and Molecular Biology, USADepartment of Biochemistry and Molecular Biology, USADepartment of Surgery, College of Medicine, USADepartment of Biochemistry and Molecular Biology, USADepartment of Biochemistry and Molecular Biology, USAOral Health Sciences, College of Dental Medicine, USADepartment of Haematology and Oncology, College of Medicine, USAHollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USAHollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USADepartment of Surgery, College of Medicine, USADepartment of Biochemistry and Molecular Biology, USA; Division of Molecular Medicine, Department of Internal Medicine, UNM Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM, 87131, USA; Corresponding author. Division of Molecular Medicine, Department of Internal Medicine, UNM Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM 87131, USAHu Antigen R, also known as ELAVL1 (HuR), is a key posttranscriptional regulator in eukaryotic cells. HuR overexpression promotes several malignancies, including head and neck squamous cell carcinoma (HNSCC). However, its immune dysfunction-associated tumorigenesis pathways remain unknown. We examined HuR's effects on oral malignancies and immune cell function in vitro and in vivo using oral carcinoma cells and transgenic HuR knockout (KO) mice. CRISPR/Cas9-mediated HuR deletion in mice syngeneic oral cancer cells eliminated colony formation and tumor development. HuR-KO tumors had a lower tumor volume, fewer CD4+CD25+FoxP3+ regulatory T cells, and more CD8+ T cells, suggesting that HuR may suppress the immune response during oral cancer progression. In contrast, HuR KO oral epithelial tissues are resistant to 4NQO-induced oral malignancies compared to control tumor-bearing mice. HuR KO mice showed fewer Tregs and greater IFN levels than WT tumor-bearing mice, suggesting anticancer activity. Finally, the HuR inhibitor pyrvinium pamoate lowers tumor burden by enhancing CD8+ infiltration at the expense of CD4+, suggesting anticancer benefits. Thus, HuR-dependent oral neoplasia relies on immunological dysfunction, suggesting that decreasing HuR may boost antitumor potential and offer a novel HNSCC therapy.http://www.sciencedirect.com/science/article/pii/S2772906024001420Oral squamous cell carcinomaRNA-Binding proteinsT-regulatory cellsPyrvinium pamoateImmune infiltrationAntitumor effects |
| spellingShingle | Mrinmoyee Majumder Harinarayanan Janakiraman Paramita Chakraborty Anitha Vijayakumar Sari Mayhue Hong Yu Toros Dincman Romeo Martin Elizabeth O'Quinn Shikhar Mehrotra Viswanathan Palanisamy RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma Oral Oncology Reports Oral squamous cell carcinoma RNA-Binding proteins T-regulatory cells Pyrvinium pamoate Immune infiltration Antitumor effects |
| title | RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma |
| title_full | RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma |
| title_fullStr | RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma |
| title_full_unstemmed | RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma |
| title_short | RNA-binding protein HuR reprograms immune T cells and promotes oral squamous cell carcinoma |
| title_sort | rna binding protein hur reprograms immune t cells and promotes oral squamous cell carcinoma |
| topic | Oral squamous cell carcinoma RNA-Binding proteins T-regulatory cells Pyrvinium pamoate Immune infiltration Antitumor effects |
| url | http://www.sciencedirect.com/science/article/pii/S2772906024001420 |
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