MiRNAs role in the biology of pancreatic cancer

MiRNAs role in the biology of pancreatic cancer
setare samizade,^1,* Alireza Nasr Isfahani,² Fatemeh Abedi dorcheh ,³ Anasik Karbedian hajiabadi ,⁴
1. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
2. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
3. Departman of Biotechnology,School of Bioscience and biotechnology,Shahid Ashrafi University Of Isfahan,Sepahan shahr,Iran
4. Department of Microbiology, School of Biological Sciences, Islamic Azad University of Falavarjan,Iran
Introduction: Pancreatic cancer (PC) is the seventh most common malignancy which is one of the deadliest cancers in the world, as a consequence of late diagnosis, early metastasis and limited response to chemotherapy. The limited efficacy of current treatments necessitates the development of novel therapeutic strategies that are based on an understanding of the molecular mechanisms involved in pancreatic cancer progression. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the expression of multiple proteins in the post-translation process which exhibit oncogenic or tumor suppressive activities by directly binding to their target messenger as advanced pancreatic therapies and have been identified to play a significant role in pancreatic cancer regulation. Profiling of deregulated miRNAs in pancreatic cancer can associate to diagnosis, indicate optimal treatment and predict response to therapy. Furthermore, understanding the main important genes in pancreatic cancer along with downstream pathways can identify possible miRNAs as therapeutic candidates.so this study aims to investigate miRNAs involvement in the biology of PC associated with their pathways.
Methods: MicroRNA specifications was accrued by using mirbase, HMDD and miRdSNP. The valid and predict genes obtained from miRTarBase, MIRWALK2.0, TargetScan and DIANA Tools. To identify common target genes between MiRNAs, Venn diagram used. GEPIA2 used to investigate gene expression in normal and pancreas tumor tissue. Finally, pathways archived from KEGG and David for genes with high expression difference. GENEMANIA was used to obtain gene network.
Results: The result dedicated that mir-202-3p ,mir-22-3p, mir-98-5p and mir-1237-3p by inhibiting Ras which actives Raf1, MEK, ERK through phosphorylation prevent proliferation of cancer cell and angiogenesis. IKK, NFkB were inhibited by blocking PI3K, which actives Ras. So MYC, BCL through inhibition cell survival, suppress cancer. Mir-199a-5p, and 3120d by inhibiting Ras, PI3K, IKK, NFkB through preventing cell cycle, prevent cancer development.
Conclusion: multiple signaling pathways are involved in the pathogenesis of PC, such as JNK, PI3K/AKT, nuclear factor kappaB (NF-κB) in which mir-202-3p mir-22-3p,mir-98-5p and mir-1237-3p by effecting on Ras, IKK, NFkB1, PI3K inhibit proliferation, angiogenesis and cell survival. Mentioned microRNAs by acting as tumor suppressor prevent cancer development and tumor spread by inhibiting proliferation of cancer cell, angiogenesis and sell survival
Keywords: Pancreatic cancer, Signaling pathways, MicroRNA, tumor suppressor