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A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis

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 physiologi...

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Autores principales: Li, Fang, Cai, Yuhan, Deng, Sihan, Yang, Lin, Liu, Na, Chang, Xiaohan, Jing, Lankai, Zhou, Yifeng, Li, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573159/
https://www.ncbi.nlm.nih.gov/pubmed/34534547
http://dx.doi.org/10.1016/j.jbc.2021.101182
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author Li, Fang
Cai, Yuhan
Deng, Sihan
Yang, Lin
Liu, Na
Chang, Xiaohan
Jing, Lankai
Zhou, Yifeng
Li, Hua
author_facet Li, Fang
Cai, Yuhan
Deng, Sihan
Yang, Lin
Liu, Na
Chang, Xiaohan
Jing, Lankai
Zhou, Yifeng
Li, Hua
author_sort Li, Fang
collection PubMed
description 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.
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spelling pubmed-85731592021-11-10 A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis Li, Fang Cai, Yuhan Deng, Sihan Yang, Lin Liu, Na Chang, Xiaohan Jing, Lankai Zhou, Yifeng Li, Hua J Biol Chem Research Article 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. American Society for Biochemistry and Molecular Biology 2021-09-14 /pmc/articles/PMC8573159/ /pubmed/34534547 http://dx.doi.org/10.1016/j.jbc.2021.101182 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Li, Fang
Cai, Yuhan
Deng, Sihan
Yang, Lin
Liu, Na
Chang, Xiaohan
Jing, Lankai
Zhou, Yifeng
Li, Hua
A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
title A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
title_full A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
title_fullStr A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
title_full_unstemmed A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
title_short A peptide CORO1C-47aa encoded by the circular noncoding RNA circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
title_sort peptide coro1c-47aa encoded by the circular noncoding rna circ-0000437 functions as a negative regulator in endometrium tumor angiogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8573159/
https://www.ncbi.nlm.nih.gov/pubmed/34534547
http://dx.doi.org/10.1016/j.jbc.2021.101182
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