Related Experiment Video
Updated: Jun 12, 2025
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Genome-wide analysis reveals the MORC3-mediated repression of PD-L1 expression in head and neck cancer
Wenxuan Fu1,2, Xiaomeng Chang1,2,3, Kun Ye1,2
1School of Stomatology, Nanchang University, Nanchang, China.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
The present study demonstrated that MORC3 regulates IFN-associated pathways and is a novel repressor of PD-L1 expression and cancer cell proliferation.
Insights
MORC3 is downregulated in cancers and represses PD-L1 expression and tumor cell growth. Its knockdown increases immune-related genes and promotes cancer proliferation, offering new therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Programmed death-ligand 1 (PD-L1) is crucial in regulating anti-tumor immunity.
- Mechanisms controlling PD-L1 expression require further investigation.
- MORC family CW-type zinc finger 3 (MORC3) influences innate immunity, but its role in cancer is unclear.
Purpose of the Study:
- To explore MORC3 expression in various cancers.
- To investigate MORC3's role in regulating PD-L1 expression and cancer cell proliferation.
Main Methods:
- RNA interference (RNAi), RNA sequencing (RNA-seq), and qRT-PCR were used in head and neck cancer cells.
- MORC3 and target gene expression were analyzed at transcriptional and translational levels.
- Analysis included single cancer cell expression.
Main Results:
- MORC3 was downregulated in multiple cancers, with low expression linked to poor survival.
- MORC3 knockdown increased immune-related genes (e.g., IFN-associated genes) and upregulated PD-L1 and STAT1.
- MORC3 knockdown promoted cancer cell proliferation and upregulated LINC00880, a lnc-RNA that influences PD-L1 expression.
Conclusions:
- MORC3 acts as a novel repressor of PD-L1 expression and cancer cell proliferation.
- MORC3 regulates interferon-associated pathways.
- MORC3's role in cancer warrants further study for therapeutic development.
More Related Videos
07:52In Vivo CRISPR/Cas9 Screening to Simultaneously Evaluate Gene Function in Mouse Skin and Oral Cavity
Published on: November 2, 2020
11:06Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
Published on: September 20, 2017
