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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Signaling
Volume 12 - 2024 |
doi: 10.3389/fcell.2024.1410130
This article is part of the Research Topic Revolutionizing Cancer Treatment: Navigating the Intricate Landscape of Cellular Signaling Networks View all 6 articles
Genome-Wide Analysis Reveals the MORC3-Mediated Repression of PD-L1 Expression in Head and Neck Cancer
Provisionally accepted- 1 School of Stomatology, Nanchang University, Jiangxi Province Key Laboratory of Oral Biomedicine, Jiangxi Province Clinical Research Center for Oral Disease, China, Nanchang City,Jiangxi Province, China
- 2 Jiangxi Province Key Laboratory of Oral Biomedicine, Nanchang City,Jiangxi Province, China
- 3 Jiangxi Province Clinical Research Center for Oral Diseases,, Nanchang City,Jiangxi Province, China
Programmed death-ligand 1 (PD-L1) plays essential roles in the negative regulation of anti-tumor immunity. However, the regulatory mechanisms of PD-L1 expression need further exploration. MORC family CW-type zinc finger 3 (MORC3) is a transcriptional factor that regulates innate immune responses, but the expression and roles of MORC3 in cancers remain largely unknown. The present study explored the expression of MORC3 in cancers at both transcriptional and translational levels. The target genes and pathways were analyzed using RNA interference (RNAi), RNA sequencing (RNA-seq), and quantitative real-time polymerase chain reaction (qRT-PCR) technology in head and neck cancer cells. The expression of MORC3 and its target genes were also analyzed in single cancer cells. MORC3 was significantly downregulated in multiple cancers, including head and neck cancer, and low expression of MORC3 was associated with poor overall survival. MORC3 knockdown significantly increased the expression of many immune-related genes, including interferon (IFN)-associated genes [MX dynamin like GTPase 2 (MX2), interferon induced protein with tetratricopeptide repeats 1 (IFIT1), interferon induced protein with tetratricopeptide repeats 2 (IFIT2), interferon regulatory factor 7 (IRF7), interferon regulatory factor 9 (IRF9), interferon induced protein 44 like (IFI44L), interferon induced transmembrane protein 1 (IFITM1), interferon induced transmembrane protein 3 (IFITM3), interferon induced protein 44 (IFI44), and interferon induced with helicase C domain 1 (IFIH1)]. MORC3 knockdown significantly upregulated PD-L1 and signal transducer and activator of transcription 1 (STAT1) expression. Moreover, the LINC00880 immune-related long non-coding RNA (lnc-RNA) was upregulated by MORC3 knockdown. Silencing LINC00880 attenuated PD-L1 expression. MORC3 knockdown also increased the expression of cellular proliferation-related genes and promoted cancer cell proliferation. In conclusion, the present study demonstrated that MORC3 regulates IFN-associated pathways and is a novel repressor of PD-L1 expression and cancer cell proliferation.
Keywords: MORC3, PD-L1, head and neck cancer, Cell Proliferation, LINC00880
Received: 31 Mar 2024; Accepted: 23 Aug 2024.
Copyright: © 2024 Fu, Chang, Ye, Zheng, Lai, Ge and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yan Shi, School of Stomatology, Nanchang University, Jiangxi Province Key Laboratory of Oral Biomedicine, Jiangxi Province Clinical Research Center for Oral Disease, China, Nanchang City,Jiangxi Province, China
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