Prediction of target gene of miR-486-5p and bioinformatics analysis of their roles in pancreatic adenocarcinoma
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R735.9

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    Abstract:

    Background and Aims: Pancreatic cancer is one of the main causes of cancer-related death. It is the most malignant tumor of the digestive system. Its main pathological type is pancreatic adenocarcinoma (PAAD), which has a dismal prognosis. MiR-486-5p plays an important role in different cancers, but there is still no research report on miR-486-5p in PAAD so far. This study was conducted to explore the target genes of miR-486-5p and analyze the expression and significance of its target genes in PAAD by bioinformatics approaches.
    Methods: The correlation between miR-486-5p and the prognosis of PAAD was analyzed using the PROGmiRV2 database. The target genes of miR-486-5p were predicted by combined use of multiple data platforms, and then, the gene ontology (GO) enrichment analysis and Kyoto Gene and Genome Encyclopedia (KEGG) signal pathway analysis were performed for the selected target genes using the DAVID online database. After that, the protein-protein interaction (PPI) network of the target genes was constructed using the STRING database, and visualized using Cytoscape software for to screen the core genes in the PPI network. Finally, the candidate genes were verified and picked up to find the core genes related to the prognosis of PAAD. 
    Results: The overall survival time of PAAD patients with low miR-486-5p expression was shorter than that of PAAD patients with high miR-486-5p expression (P<0.05). A total of 187 target genes were obtained, which were predicted by at least 3 different databases. Go analysis showed that the predicted target genes were mainly involved in the biological processes such as protein stability, protein phosphorylation, positive regulation of RNA polymerase II promoter transcription and negative regulation of apoptosis; KEGG analysis showed that the target genes were mainly involved in FOXO signaling pathway, p53 signal pathway, Ras signaling pathway, and PI3K-Akt signaling pathway. Protein network analysis of potential target genes of miR-486-5p showed that SIRT1, PTEN, SMAD2, CSNK2A1 and SERPINE1 were key target genes in PPI network. Further GEPIA verification revealed that CSNK2A1 and SERPINE1 were significantly up-regulated in PAAD tissues (all P<0.05). The high expressions of these genes were associated with the overall and disease-free survival in patients with PAAD (all P<0.05), and those with high expressions of CSNK2A1 and SERPINE1 had worse prognosis.
    Conclusion: MiR-486-5p acts on the network of multiple signaling pathways in PAAD patients through the regulation of targeted genes, participates in the occurrence and development of PAAD, and affects the prognosis of PAAD patients.

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REN Tianyu, ZHOU Xintong, DANG Shengchun. Prediction of target gene of miR-486-5p and bioinformatics analysis of their roles in pancreatic adenocarcinoma[J]. Chin J Gen Surg,2020,29(6):715-722.
DOI:10.7659/j. issn.1005-6947.2020.06.012

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History
  • Received:August 28,2019
  • Revised:August 28,2019
  • Adopted:
  • Online: June 25,2020
  • Published: