miR-155-5p is Negatively Associated with Acute Pancreatitis and Inversely Regulates Pancreatic Acinar Cell Progression by Targeting Rela and Traf3
Autor: | Ning Ning, Le Wang, Xianhai Mao, Hao Li, Honglian Zou, Yonggang Wang, Yu Jiang, Chen Chen, Meifu Chen, Sulai Liu, Chuang Peng, Bo Jiang, Xiaohui Duan, Wei Cheng, Hongying Tang |
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Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine Physiology Acinar Cells Biology lcsh:Physiology Cell Line lcsh:Biochemistry miR-155 03 medical and health sciences chemistry.chemical_compound microRNA Acinar cell medicine Animals Humans lcsh:QD415-436 Aged lcsh:QP1-981 TNF Receptor-Associated Factor 3 Traf3 Transcription Factor RelA Rela Transfection Middle Aged medicine.disease Acute pancreatitis Rats Mice Inbred C57BL MicroRNAs 030104 developmental biology Real-time polymerase chain reaction Gene Expression Regulation Pancreatitis chemistry MAP Cancer research Female miR-155-5P Transcriptome SAP Helenalin |
Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 4, Pp 1584-1599 (2018) |
ISSN: | 1421-9778 1015-8987 |
Popis: | Background/Aims: Acute pancreatitis contributes to high mortality in pancreatitis patients, and miRNAs play a vital role in the development of acute pancreatitis (AP), however, its precise biological role remains largely elusive. Methods: To clarify the potential mechanisms of miRNAs in AP, we built mouse models of mild acute pancreatitis (MAP) and moderate/ severe acute pancreatitis (SAP). MiRNA microarray analysis and Real-time quantitative PCR (qRT-PCR) were used to analyze the expression of miRNA in MAP/SAP. TargetScan software, dual-luciferase gene reporter assays and Western blotting were used to assess the target genes of miR-155-5p in AP. Results: miR-155-5p was significantly decreased in MAP/SAP mice compared to controls. In pancreatic acinar AR42J cells transfected with miR-155-5p mimic, the expression of Rela and Traf3 notably decreased in both the caerulein- and TLC-S-induced groups compared with the negative control (NC); however, the expression of Rela and Traf3 notably increased after transfection with miR-155-5p inhibitor. Combined analysis using the TargetScan software and dual-luciferase gene reporter assays indicated that Rela and Traf3 were both targeted by miR-155-5p. Meanwhile, the expression of Ptgs2 also decreased after transfection of the AR42J cells with miR-155-5p mimic. The opposite results were found when miR-155-5p inhibitor was transfected into the AR42J cells. In addition, we treated caerulein- and TLC-S-induced AR42J cells with the Rela inhibitor helenalin and found that the expression of Rela, Traf3 and Ptgs2 decreased compared with the NC, while the expression of miR-155-5p did not show any significant difference. Furthermore, we found that miR-155-5p was significantly down-regulated in pancreatitis patients. Conclusion: miR-155-5p inversely regulated AP development through the Rela/Traf3/Ptgs2 signaling pathway. |
Databáze: | OpenAIRE |
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