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Updated: Mar 18, 2026
Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
Evaluation of genetic variation in tumor suppressor miRNA encoding and their target genes in breast cancer; focus on
Yogita Chhichholiya1, Sandeep Singh1, Rajesh Vashistha2
1Department of Human Genetics and Molecular Medicine, Central University of Punjab Bathinda, Bathinda, Punjab, India.
Background:
Genetic variations in tumor suppressor miRNAs and the 3'UTR of their target genes influence tumor biology and breast cancer (BC) risk.
Objective:
This 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.
Methods:
The 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.
Results:
Two 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.
Conclusion:
Variants 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.
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