miR-412-5p targets Xpo1 to regulate angiogenesis in hemorrhoid tissue
| Autor: | Chunsheng Luo, Te Liu, Chen Wang, Chengkun Song, Qingming Wang, Yunhua Peng, Wei Yang, Yaojie Xin, Hong Lu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Src Homology 2 Domain-Containing Transforming Protein 1 Angiogenesis Down-Regulation Receptors Cytoplasmic and Nuclear Endogeny Biology Karyopherins Hemorrhoids Umbilical vein Pathogenesis 03 medical and health sciences Genomic Imprinting 0302 clinical medicine Downregulation and upregulation Cell Movement microRNA Genetics Human Umbilical Vein Endothelial Cells Humans 3' Untranslated Regions Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation Cell Nucleus Neovascularization Pathologic General Medicine Middle Aged In vitro Cell biology Endothelial stem cell MicroRNAs 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Female Tumor Suppressor Protein p53 Signal Transduction |
| Zdroj: | Gene. 705 |
| ISSN: | 1879-0038 |
| Popis: | Hemorrhoid is a common and recurrent proctological disease, which is often accompanied by angiogenesis and edema. MicroRNAs in the DLK1-DIO3 imprinted clusters are involved in the development and pathogenesis of mammalian hemorrhoids. Results of the present study indicated multiple, differential expression of DLK1-DIO3 imprinted cluster microRNA between hemorrhoid and normal tissues, where miR-412-5p expression in hemorrhoid tissue was significantly decreased. Fluorescein reporter assays showed that miR-412-5p silenced Xpo1 mRNA expression by targeting its 3'-UTR. Overexpression of miR-412-5p in human umbilical vein endothelial cells (HUVECs) indicated that proliferation, migration and formation of vascular structures in HUVECs were inhibited in vitro. In addition, overexpression of miR-412-5p significantly inhibited Xpo1 expression and promoted upregulation of the p53 protein and its retention in the nucleus. Simultaneously, expression of p66SHC and p16 proteins was activated. In summary, downregulation of endogenous miR-412-5p expression in hemorrhoid vascular endothelial cells leads to high expression of the target gene Xpo1 and translocation of the p53 protein out of the nucleus, rendering it unable to activate p66SHC and p16. This ultimately weakens regulation of the vascular endothelial cell cycle, thereby accelerating the division of hemorrhoid vascular endothelial cells, leading to angiogenesis. |
| Databáze: | OpenAIRE |
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