The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation
| Autor: | Zheng Pang, Yao Liu, Jian Tu, Yue-Xiang Ren, Xiao-Dong Sun, Jian-Ming Li, Zheng Zhi, Lian Wang, Liang-Yan Chen, Yan Qin, Li-Na Sun |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms Angiogenesis miRNA sponge Mice Nude Apoptosis Biology Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Movement Circular RNA Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans RNA Messenger miR-138 Adaptor Proteins Signal Transducing Cell Proliferation Mice Inbred BALB C Gene knockdown Messenger RNA hypoxia Research EIF4E RNA Circular Hypoxia-Inducible Factor 1 alpha Subunit Prognosis medicine.disease Colorectal cancer Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Blot MicroRNAs 030104 developmental biology Oncology Protein Biosynthesis 030220 oncology & carcinogenesis Cancer research Molecular Medicine Colorectal Neoplasms |
| Zdroj: | Molecular Cancer |
| ISSN: | 1476-4598 |
| DOI: | 10.1186/s12943-020-01272-9 |
| Popis: | Background Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive. Methods qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circ-ERBIN. Function-based experiments were performed using circ-ERBIN overexpression and knockdown cell lines in vitro and in vivo, including CCK8, colony formation, EdU assay, transwell, tumor growth and metastasis models. Mechanistically, luciferase reporter assay, western blots and immunohistochemical stainings were performed. Results Circ-Erbin was highly expressed in the CRC cells and Circ-Erbin overexpression facilitated the proliferation, migration and metastasis of CRC in vitro and in vivo. Notably, circ-Erbin overexpression significantly promoted angiogenesis by increasing the expression of hypoxia induced factor (HIF-1α) in CRC. Mechanistically, circ-Erbin accelerated a cap-independent protein translation of HIF-1α in CRC cells as the sponges of miR-125a-5p and miR-138-5p, which synergistically targeted eukaryotic translation initiation factor 4E binding protein 1(4EBP-1). Conclusions Our findings uncover a key mechanism for circ-Erbin mediated HIF-1α activation by miR-125a-5p-5p/miR-138-5p/4EBP-1 axis and circ-ERBIN is a potential target for CRC treatment. |
| Databáze: | OpenAIRE |
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