Granzyme mRNA-miRNA interaction and its implication to functional impact

Hyeon-Young Kim; Jung-Min Kim; Young Kee Shin

doi:10.1007/s13258-024-01578-8

Granzyme mRNA-miRNA interaction and its implication to functional impact

Genes Genomics. 2024 Nov 12. doi: 10.1007/s13258-024-01578-8. Online ahead of print.

Authors

Hyeon-Young Kim^#¹, Jung-Min Kim^#², Young Kee Shin^{3

4}

Affiliations

¹ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea.
² Department of Integrated Biological Science, Pusan National University, Busan, 46241, Republic of Korea.
³ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 08826, Republic of Korea. ykeeshin@snu.ac.kr.
⁴ Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. ykeeshin@snu.ac.kr.

^# Contributed equally.

PMID: 39528794
DOI: 10.1007/s13258-024-01578-8

Abstract

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.

Keywords: Cancer; Gene expression; Granzyme; Transcription factor; miRNA.