A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
| Autor: | Chang Xiaohan, Fang Li, Lin Yang, Na Liu, Hua Li, Yifeng Zhou, Sihan Deng, Lankai Jing, Cai Yuhan |
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| Rok vydání: | 2021 |
| Předmět: |
Aryl hydrocarbon receptor nuclear translocator
Angiogenesis EC endometrial cancer circRNA circular RNA Mice Nude Biology Biochemistry angiogenesis mRNP mRNA-protein particle Circular RNA IRES internal ribosomal entrance site Gene expression Animals Humans RNA Neoplasm TACC3 transforming acidic coiled-coil 3 Molecular Biology Transcription factor Mice Inbred BALB C Neovascularization Pathologic functional peptide Microfilament Proteins RNA RNA Circular Cell Biology hsa-circ-0000437 Non-coding RNA VEGF Endometrial Neoplasms Neoplasm Proteins sORF short open reading frame Cell biology Gene Expression Regulation Neoplastic ChIP chromatin immunoprecipitation Open reading frame endometrial cancer Female Peptides Research Article ncRNA noncoding RNA OE overexpression |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.101182 |
| Popis: | Circular RNAs (circRNAs) are a novel class of widespread noncoding RNAs that regulate gene expression in mammals. Recent studies demonstrate that functional peptides can be encoded by short open reading frames in noncoding RNAs, including circRNAs. However, the role of circRNAs in various physiological and pathological states, such as cancer, is not well understood. In this study, through deep RNA sequencing on human endometrial cancer (EC) samples and their paired adjacent normal tissues, we uncovered that the circRNA hsa-circ-0000437 is significantly reduced in EC compared with matched paracancerous tissue. The hsa-circ-0000437 contains a short open reading frame encoding a functional peptide termed CORO1C-47aa. Overexpression of CORO1C-47aa is capable of inhibiting angiogenesis at the initiation stage by suppressing endothelial cell proliferation, migration, and differentiation through competition with transcription factor TACC3 to bind to ARNT and suppress VEGF. CORO1C-47aa directly bound to ARNT through the PAS-B domain, and blocking the association between ARNT and TACC3, which led to reduced expression of VEGF, ultimately lead to reduced angiogenesis. The antitumor effects of CORO1C-47aa on EC progression suggest that CORO1C-47aa has potential value in anticarcinoma therapies and warrants further investigation. |
| Databáze: | OpenAIRE |
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