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Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia

Circular RNAs (circRNAs), a novel family of non-coding RNAs, play crucial roles in cancer progression. While the existing research focuses on nuclear genome-derived (nu)-circRNAs, the biological and clinical characteristics of mitochondrial genome-derived (mt)-circRNAs remain largely unknown, especi...

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Autores principales: Wu, Zijuan, Sun, Handong, Wang, Chunling, Liu, Wenjie, Liu, Ming, Zhu, Yanhui, Xu, Wei, Jin, Hui, Li, Jianyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240210/
https://www.ncbi.nlm.nih.gov/pubmed/32438315
http://dx.doi.org/10.1016/j.omtn.2020.04.017
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author Wu, Zijuan
Sun, Handong
Wang, Chunling
Liu, Wenjie
Liu, Ming
Zhu, Yanhui
Xu, Wei
Jin, Hui
Li, Jianyong
author_facet Wu, Zijuan
Sun, Handong
Wang, Chunling
Liu, Wenjie
Liu, Ming
Zhu, Yanhui
Xu, Wei
Jin, Hui
Li, Jianyong
author_sort Wu, Zijuan
collection PubMed
description Circular RNAs (circRNAs), a novel family of non-coding RNAs, play crucial roles in cancer progression. While the existing research focuses on nuclear genome-derived (nu)-circRNAs, the biological and clinical characteristics of mitochondrial genome-derived (mt)-circRNAs remain largely unknown, especially in chronic lymphocytic leukemia (CLL). In this study, we attempted to identify the novel characteristics of mc-COX2 (mitochondrial genome-derived circRNAs [mc]), one of the mt-circRNAs that can be involved in CLL progression. mt-circRNAs were found to be highly expressed in the plasma exosomes of CLL patients. The endogenous reduction of mc-COX2 can affect mitochondrial functions, suppress cell proliferation, and induce cell apoptosis. The upregulation of mc-COX2 was positively associated with leukemogenesis and worsening survival of CLL patients. Notably, functional analysis revealed that mc-COX2, as differing from conventional nu-circRNAs, was less stable and may function through novel mechanisms other than acting as the competing endogenous RNA. We also screened and tested several chemical compounds and small-molecule inhibitors that can decrease the generation of mc-COX2. It was found that the silencing of mc-COX2 in CLL cells strengthened the anti-tumor effects of drugs used in coordination. Our findings prove that mc-COX2, a critical mt-circRNA highly expressed in plasma, derived from CLL cells and delivered by exosomes, is associated with the progression and prognosis of CLL.
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spelling pubmed-72402102020-05-26 Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia Wu, Zijuan Sun, Handong Wang, Chunling Liu, Wenjie Liu, Ming Zhu, Yanhui Xu, Wei Jin, Hui Li, Jianyong Mol Ther Nucleic Acids Article Circular RNAs (circRNAs), a novel family of non-coding RNAs, play crucial roles in cancer progression. While the existing research focuses on nuclear genome-derived (nu)-circRNAs, the biological and clinical characteristics of mitochondrial genome-derived (mt)-circRNAs remain largely unknown, especially in chronic lymphocytic leukemia (CLL). In this study, we attempted to identify the novel characteristics of mc-COX2 (mitochondrial genome-derived circRNAs [mc]), one of the mt-circRNAs that can be involved in CLL progression. mt-circRNAs were found to be highly expressed in the plasma exosomes of CLL patients. The endogenous reduction of mc-COX2 can affect mitochondrial functions, suppress cell proliferation, and induce cell apoptosis. The upregulation of mc-COX2 was positively associated with leukemogenesis and worsening survival of CLL patients. Notably, functional analysis revealed that mc-COX2, as differing from conventional nu-circRNAs, was less stable and may function through novel mechanisms other than acting as the competing endogenous RNA. We also screened and tested several chemical compounds and small-molecule inhibitors that can decrease the generation of mc-COX2. It was found that the silencing of mc-COX2 in CLL cells strengthened the anti-tumor effects of drugs used in coordination. Our findings prove that mc-COX2, a critical mt-circRNA highly expressed in plasma, derived from CLL cells and delivered by exosomes, is associated with the progression and prognosis of CLL. American Society of Gene & Cell Therapy 2020-05-01 /pmc/articles/PMC7240210/ /pubmed/32438315 http://dx.doi.org/10.1016/j.omtn.2020.04.017 Text en © 2020 The Authors http://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 Article
Wu, Zijuan
Sun, Handong
Wang, Chunling
Liu, Wenjie
Liu, Ming
Zhu, Yanhui
Xu, Wei
Jin, Hui
Li, Jianyong
Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia
title Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia
title_full Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia
title_fullStr Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia
title_full_unstemmed Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia
title_short Mitochondrial Genome-Derived circRNA mc-COX2 Functions as an Oncogene in Chronic Lymphocytic Leukemia
title_sort mitochondrial genome-derived circrna mc-cox2 functions as an oncogene in chronic lymphocytic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240210/
https://www.ncbi.nlm.nih.gov/pubmed/32438315
http://dx.doi.org/10.1016/j.omtn.2020.04.017
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