Determination of Novel miRNA-target Interactions in Endometrial Cancer Using Network Analysis

Determination of Novel miRNA-target Interactions in Endometrial Cancer Using Network Analysis
Hossein Ghahramani almanghadim,¹ Sedigheh Sadat Mortazavi ,² Zahra Bahmanpour ,³ Zinat Shams ,⁴ Maryam Shahali ,^5,*
1. Department of Molecular Genetics, Faculty of Basic Sciences, Islamic Azad University, Ahar Branch, Ahar, Iran
2. Division of Genetics, Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran
3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
4. Biochemistry Department of Biological science, kharazmi university Tehran, Iran
5. Production Department, Research and Production Complex Pasteur Institute of Iran, Tehran, Iran
Introduction: Endometrial cancer (EC) is considered as one of the most common cancer in women with 380,000 new cases wordwide every year. In addirion, EC is known as a disease which mainly affects postmenopausal women (more than 90% with the age above 50 years). The current classification of endometrioid adenocarcinoma is only based on the histology which directs subsequent therapeutic management. However, the approach is often insufficient for prognosis. Therefore, new approaches should be developed to identify and characterize novel biomarkers for understanding different subtypes better, improving prognosis assessment, and optimizing patient care. MicroRNAs are particularly attractive candidates as biomarkers.
Methods: Microarray data in Gene Expression Omnibus (GEO) was used to obtain the EC-involved miRNA. Then, MiRSystem, as an integrated system for predicting target mRNAs and their associated pathway, was applied to find significant pathways. Subsequently, the genes of these pathway were selected and the miRNAs regulating these genes were determined. Further, Venn diagram was utilized to calculate the intersection of the list of elements. Finally, miRNA-target interactions were visualized by Cytoscape.
Results: the findings revealed that four miRNAs ("miR-103a-3p", "miR-107", "miR-424-5p", and "miR-497-5p") involved in the mitogen-activated protein kinases (MAPK) signal pathways. Moreover, according to the result of the Venn diagram represented the association between three genes (RPS6KA3, NTRK2, MAP3K3) with the miRNAs.
Conclusion: Based on the results, the miR analysis of endometrial tumor tissue complements the classical anatomo-pathological approach and adds prognostic and therapeutic value.
Keywords: Biomarker, Endometrial cancer, In silico analysis, miRNAs