Exploring Non-Canonical DNA Structures in Promoter Regions of Cancer- Associated Genes and Their Role in Regulating Gene Expression
DOI:
https://doi.org/10.31185/bsj.Vol23.Iss47.1646Keywords:
: G-quadruplex, promoter region, gene regulation, cancer genes, bioinformatics, transcriptionAbstract
This study investigated non-canonical DNA secondary structures of the G-quadruplex (G4) type within the promoter regions of selected cancer-associated genes and compared them with housekeeping control genes using bioinformatics tools. Promoter sequences extending 1000 base pairs upstream of the transcription start site (TSS) were retrieved for ten cancer-related genes, namely MYC, TP53, KRAS, EGFR, BCL2, BRAF, PTEN, PIK3CA, NRAS, and CDKN2A, as well as six housekeeping genes, GAPDH, ACTB, HPRT1, RPL13A, TBP, and YWHAZ, from the human genome reference GRCh38/hg38 via the UCSC Genome Browser. The sequences were then analyzed using QGRS Mapper to predict potential G4-forming sequences and calculate their corresponding score-G values.
The results showed clear differences between the two groups in terms of the number, density, and predicted structural strength of G4 motifs. Promoter regions of cancer-associated genes appeared richer in G4 structures and exhibited higher score-G values than housekeeping genes. A considerable proportion of these motifs was located near the TSS, particularly in MYC, KRAS, NRAS, and EGFR, suggesting a potential direct regulatory role in gene expression. In contrast, housekeeping genes showed a weaker, less dense, and more dispersed G4 pattern across the promoter region.
Overall, the findings support the hypothesis that promoter G4 structures may constitute an important regulatory element in cancer-associated genes, with their positional distribution and structural stability potentially linked to transcriptional control. These structures may therefore contribute to a deeper understanding of gene regulation and provide a basis for future experimental studies aimed at evaluating their therapeutic potential
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