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Evaluation of genetic variation in tumor suppressor miRNA encoding and their target genes in breast cancer; focus on miRNA interaction and expression analysis
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DOI：10.3389/fgeed.2026.1705463.png)
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Abstract
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BackgroundGenetic variations in tumor suppressor miRNAs and the 3′UTR of their target genes influence tumor biology and breast cancer (BC) risk.ObjectiveThis study investigated genetic variations in tumor suppressor miRNAs (hsa-let-7c; hsa-miR-34a; hsa-miR-145a) and their target genes (KRAS; IGFBP6; IGF1R); and their functional significance in BC patients.MethodsThe miRNA encoding regions and 3′UTRs of the selected target genes were sequenced in 208 BC patients. Functional analyses were performed using luciferase assay; RT-PCR; IHC; and Western blotting. RNAfold; TNM plot; Kaplan-Meier Plotter; and ROC Plotter were used for structural predictions; survival; and therapy response analysis.ResultsTwo variants; rs712 and rs9266; were found in the 3′UTR of KRAS. Luciferase assay confirmed that rs9266 disrupts the binding of hsa-let-7c and hsa-miR-181c; leading to increased KRAS expression. KRAS expression was highest in heterozygous; followed by homozygous mutant; and lowest in wild-type genotypes. Higher hsa-let-7c and hsa-miR-181c expression correlated with better survival. ROC analysis identified KRAS as a potential predictive biomarker for chemotherapy response.ConclusionVariants rs712 and rs9266 in the KRAS 3′UTR impair miRNA binding; enhancing KRAS expression and tumorigenesis; while elevated hsa-let-7c and hsa-miR-181c levels predict favourable survival outcomes in BC patients.
Keywords:
breast cancer
KRAS
3′UTR
hsa-let-7c
hsa-miR-181c
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