MicroRNAs 1234-3p and hsa-mir-382-5p Prevent Progression Of Proliferation and Tumor Spread by Targeting Oncogenic Genes in Glioma

MicroRNAs 1234-3p and hsa-mir-382-5p Prevent Progression Of Proliferation and Tumor Spread by Targeting Oncogenic Genes in Glioma
Alireza Nasr Isfahani,^1,* Setare Samizadeh,² Anasik Karbedian hajiabadi,³ Fatemeh Abedi dorcheh,⁴
1. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
2. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
3. Department of Microbiology, School of Biological Sciences, Islamic Azad University of Falavarjan,Iran
4. Departman of Biotechnology,School of Bioscience and biotechnology,Shahid Ashrafi University Of Isfahan,Sepahan shahr,Iran
Introduction: Glioma is the most common primary intracranial tumor, representing 81% of malignant brain tumors. Histologically, it shares specifications of normal glial cells and are generally named according to these similarities. However, whether gliomas cause from normal glial cells, glial or neural precursors, stem cells, or other cell types remains a topic of investigation. Tremendous progress in genomic, transcriptomic and epigenetic profiling has resulted in new concepts of classifying and treating gliomas. Therefore investigating the molecular targets of glioma is necessary for designing new therapeutic agents that will improve survival rate. MiRNAs are small noncoding RNAs (19–22 nucleotides) that post translationally regulate gene expression by causing mRNA degradation or inhibiting their translation through RNA interference. So this study purposes to evaluate the association between hsa-mir-1234-3p, hsa-mir-382-5p and glioma in pathways.
Methods: Specifications of miRNAs were obtained through mirbase, HMDD and miRdSNP. To identifying target genes, miRTarBase, MIRWALK2.0, TargetScan, DIANA Tools were used. Venn diagram used to identify common target genes between MiRNAs. GEPIA2 used to investigate gene expression in normal and brain tumor tissue. The signaling pathways for target genes which had high expression difference were observed from the DAVID database and the pathways associated with glioma were stored for interpretation. The network of genes was obtained from GENE MANIA.
Results: The result demonstrated that hsa-mir-1234-3p, hsa-mir-382-5p prevent cell growth and proliferation by activating PETEN which blocks AKT. In other side of the pathway mentioned microRNAs inhibit MTOR by blocking PI3KACT and AKT and effect on adhesion increasing by preventing cell survival and proliferation by blocking BRAF and RAS which active MEK1/2, ERK1/2 , RAF and BCL2 through phosphorylation and suppresses cancer.
Conclusion: hsa-mir-1234-3p and hsa-mir-382-5p act as tumor suppressor by inhibiting angiogenesis, proliferation and effect on adhesion increasing by preventing cell migration through inhibiting AKT BRAF,RAS and up regulating PETEN in PI3KAKT, neurotrophin ,ErbB and MAPK pathways.
Keywords: Glioma, Signaling pathways, MicroRNA, Oncogenic genes