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Published on: May 21, 2019
In Silico Identification of Dysregulated miRNAs Targeting KRAS Gene in Pancreatic Cancer
Asbiel Felipe Garibaldi-Ríos1,2, Luis E Figuera1,2, Guillermo Moisés Zúñiga-González3
1División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara 44340, Jalisco, Mexico.
Abstract:
Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified dysregulated miRNAs in PC; TargetScan, miRDB, and PolymiRTS 3.0 identified miRNAs specific for the KRAS gene; and OncomiR evaluated the association of miRNAs with clinical characteristics and survival in PC. The correlation between miRNAs and KRAS was analysed using ENCORI/starBase. A total of 210 deregulated miRNAs were identified in PC (116 overexpressed and 94 underexpressed). In total, 16 of them were involved in the regulation of KRAS expression and 9 of these (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p and hsa-miR-885-5p) were associated with the clinical characteristics of the PC. Specifically, the overexpression of hsa-miR-30a-5p was associated with PC mortality, and hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p were associated with survival. Correlation analysis revealed that the expression of 10 miRNAs is correlated with KRAS expression. The dysregulated miRNAs identified in PC may regulate KRAS and some are associated with clinically relevant features, highlighting their potential as biomarkers and therapeutic targets in PC treatment. However, experimental validation is required for confirmation.
Insights
This study identified microRNAs (miRNAs) that regulate KRAS in pancreatic cancer (PC). Some of these miRNAs are linked to PC
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Pancreatic cancer (PC) has a high mortality rate, with KRAS mutations present in up to 95% of cases.
- MicroRNAs (miRNAs) show an inverse correlation with KRAS expression, suggesting their potential as diagnostic and prognostic biomarkers.
Purpose of the Study:
- To identify specific miRNAs that target KRAS.
- To investigate the association between these miRNAs and the clinical characteristics and survival outcomes in pancreatic cancer patients.
Main Methods:
- Utilized in silico methods, including databases like dbDEMC, TargetScan, miRDB, PolymiRTS 3.0, and OncomiR.
- Analyzed miRNA-KRAS correlation using ENCORI/starBase.
- Evaluated associations with clinical features and survival in PC.
Main Results:
- Identified 210 deregulated miRNAs in PC (116 overexpressed, 94 underexpressed).
- Found 16 miRNAs involved in KRAS regulation, with 9 associated with PC clinical characteristics (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p, hsa-miR-885-5p).
- Overexpression of hsa-miR-30a-5p linked to PC mortality; hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p associated with survival. Ten miRNAs showed correlation with KRAS expression.
Conclusions:
- Dysregulated miRNAs in PC can potentially regulate KRAS.
- These miRNAs are associated with clinically relevant features, indicating their potential as biomarkers and therapeutic targets for pancreatic cancer.
- Experimental validation is necessary to confirm these findings.
