Screening and analysis of single nucleotide polymorphism in the 3′-UTR microRNA target regions and its implications for lung tumorigenesis

Abstract

Aim: The study aims to identify high-impact single nucleotide polymorphisms (SNPs) in miRNA target sites of genes associated with lung cancer. Materials & methods: Lung cancer genes were obtained from Uniprot KB. miRNA target site SNPs were mined from MirSNP, miRdSNP and TargetScan. SNPs were shortlisted based on binding impact, minor allele frequency and conservation. Gene expression was analyzed in genes with high-impact SNPs in healthy versus lung cancer tissue. Additionally, enrichment, pathway and network analyzes were performed. Results: 19 high-impact SNPs were identified in miRNA target sites of lung cancer-associated genes. These SNPs affect miRNA binding and gene expression. The genes are involved in key cancer related pathways. Conclusion: The identified high-impact miRNA target site SNPs and associated genes provide a starting point for case–control studies in lung cancer patients in different populations.

Summary points

• The study aims to identify high-impact single nucleotide polymorphisms (SNPs) in microRNA (miRNA) target sites of genes associated with lung cancer.

Data collection

• Genes involved in lung cancer were retrieved from the UniProt Knowledge Base.

SNP identification

• miRNA target site SNPs were mined from databases such as MirSNP, miRdSNP and TargetScan.

Selection criteria

• SNPs were shortlisted based on their impact on miRNA binding, minor allele frequency (MAF) and conservation.

Gene expression analysis

• The expression of genes with high-impact SNPs was analyzed in healthy versus lung cancer tissues.

Bioinformatics analysis

• Enrichment, pathway and network analyses were performed to understand the biological implications of these SNPs.

Results

• High-Impact SNPs: 19 high-impact SNPs were identified in miRNA target sites of lung cancer-associated genes.

Gene expression

• These SNPs affect miRNA binding and gene expression, with the genes involved in key cancer-related pathways.

Functional analysis

• The study provided insights into the molecular functions and biological processes affected by these SNPs, including phosphotransferase and kinase activities, cell death and cell cycle regulation.

Network analysis

• Gene network analysis showed relevant interactions among the genes with high-impact SNPs, indicating their role in lung cancer pathways.

Conclusion

• The identified high-impact miRNA target site SNPs and associated genes offer a starting point for case-control studies in lung cancer patients across different populations. These findings could enhance the understanding of disease development and susceptibility in lung cancer.

Significance

• The study highlights the importance of miRNA target site SNPs in lung cancer and suggests that these SNPs could serve as potential biomarkers for disease progression and susceptibility, aiding in the development of personalized treatment strategies.

Future directions

• The study encourages further experimental validation and clinical application of the identified SNPs as biomarkers for lung cancer. It also suggests the need for randomized trials to explore the therapeutic potential of miRNA-mediated interventions in cancer treatment.

Keywords: :

• LUAD
• lung cancer
• microRNAs
• miRNA target site
• miRNA target site SNPs (miR-TS-SNPs)
• miRSNPs
• network analysis
• pathway enrichment
• single nucleotide polymorphisms (SNPs)

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/14622416.2024.2355864

Author contributions

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Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.