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Updated: Jun 7, 2025
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
Granzyme mRNA-miRNA interaction and its implication to functional impact
Hyeon-Young Kim1, Jung-Min Kim2, Young Kee Shin3,4
1Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.
Background:
Granzyme activity can affect the processing and stability of miRNAs within target cells. They also could induce changes in miRNA expression that impact apoptotic signaling. Granzyme-induced apoptosis might result in changes to the miRNA profile, which can further influence the apoptosis and inflammation processes.
Objective:
The aim of this study was to bioinformatically analyze which miRNAs and transcription factors bind to the CDS and UTR regions of the granzyme family to regulate gene expression in relation to granzyme evolution and their association with human cancer diseases.
Methods:
The expression patterns of granzyme genes were analyzed in various human tissues. MiRNAs binding to the CDS and UTR of the granzyme family were examined, and the transcription factors binding to these miRNAs binding sites were also analyzed. Cytoscape program was used to visualize and analyze the networks of interactions between granzyme mRNA and miRNAs. Additionally, the evolutionary patterns of the granzyme family in relation to miRNAs and transcription factors binding were investigated.
Results:
Analysis of the expression patterns of the granzyme family in various human tissues shows that GZMA and GZMK are strongly expressed in lymph nodes. GZMB exhibits strong expression in the bone marrow, while GZMA is prominently expressed in the spleen. Twenty-two miRNAs bind to both GZMK and GZMB mRNA, while six miRNAs bind to both GZMK and GZMM mRNA. The only miRNA that binds to GZMK, GZMB, GZMM, and GZMA mRNA is hsa-miR-146a-5p. Transcription factors JUND, FOS, and JUN are distinctly interconnected with has-miR-5696 and GZMK. Association data between the granzyme family and cancers showed that various miRNAs were consistently implicated and exhibited either upregulation or downregulation.
Conclusion:
Although the granzyme family possesses distinct genetic information, it shows relatively high expression levels in the lymph node, spleen, and bone marrow. Many miRNAs specifically regulate granzyme gene expression, and various transcription factors are involved. Analyzing the granzyme genes-miRNAs-transcription factors-related network will provide crucial insights into the mechanisms of cancer development and suppression.
Insights
This study reveals that specific microRNAs (miRNAs) and transcription factors regulate granzyme gene expression, impacting cancer development. Understanding these granzyme-miRNA-transcription factor networks is key to cancer suppression and treatment strategies.
Area of Science:
- Immunology and Molecular Biology
- Cancer Genomics and Bioinformatics
Background:
- Granzyme activity influences microRNA (miRNA) processing, stability, and expression, potentially affecting apoptotic signaling and inflammation.
- Granzyme-induced apoptosis can alter miRNA profiles, further modulating apoptosis and inflammatory responses.
Purpose of the Study:
- To bioinformatically analyze miRNA and transcription factor interactions with granzyme gene coding (CDS) and untranslated regions (UTR).
- To investigate the role of these interactions in granzyme gene regulation, evolution, and association with human cancers.
Main Methods:
- Analysis of granzyme gene expression patterns across human tissues.
- Identification of miRNAs and transcription factors binding to granzyme mRNA regions.
- Network visualization and analysis using Cytoscape.
- Investigation of evolutionary patterns of granzyme family interactions.
Main Results:
- GZMA and GZMK show high expression in lymph nodes; GZMB in bone marrow; GZMA in spleen.
- hsa-miR-146a-5p is the sole miRNA binding to GZMK, GZMB, GZMM, and GZMA mRNA.
- Specific transcription factors (JUND, FOS, JUN) interconnect with has-miR-5696 and GZMK.
- Cancer association data revealed consistent miRNA involvement with granzyme family genes, showing upregulation or downregulation.
Conclusions:
- The granzyme family exhibits high expression in immune-related tissues (lymph node, spleen, bone marrow).
- Numerous miRNAs and transcription factors specifically regulate granzyme gene expression.
- Elucidating the granzyme-miRNA-transcription factor network offers critical insights into cancer development and suppression mechanisms.
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