Cargando…
Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma
Hypoxia is a common feature of solid tumors and has been associated with tumor aggressiveness and poor prognosis. Exosomes are involved in mediating cellular-environment interactions. Circular RNAs (circRNAs) are a class of non-coding RNA broadly found in cells and exosomes. However, the functions a...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875767/ https://www.ncbi.nlm.nih.gov/pubmed/33614250 http://dx.doi.org/10.1016/j.omtn.2021.01.019 |
_version_ | 1783649830069862400 |
---|---|
author | Xu, Li Liao, Wei-Lin Lu, Qi-Jue Zhang, Peng Zhu, Ji Jiang, Ge-Ning |
author_facet | Xu, Li Liao, Wei-Lin Lu, Qi-Jue Zhang, Peng Zhu, Ji Jiang, Ge-Ning |
author_sort | Xu, Li |
collection | PubMed |
description | Hypoxia is a common feature of solid tumors and has been associated with tumor aggressiveness and poor prognosis. Exosomes are involved in mediating cellular-environment interactions. Circular RNAs (circRNAs) are a class of non-coding RNA broadly found in cells and exosomes. However, the functions and regulatory mechanisms of exosomal circRNAs induced by hypoxia remain poorly understood in lung adenocarcinoma (LUAD) development. Differentially expressed circRNAs were identified between exosomes extracted from hypoxic and normoxic conditions through microarray analysis. We focused on hsa-circ-0003439 found on chromosome 1 and derived from SET domain bifurcated histone lysine methyltransferase 1 (SETDB1), and thus we named it circSETDB1. We discovered that exosomes obtained from hypoxic LUAD cells improved the migration, invasion, and proliferation capacity of normoxic LUAD cells. circSETDB1 was found to be significantly upregulated in hypoxia-induced exosomes from LUAD cell lines compared with exosomes in the normal condition. Moreover, knockdown of circSETDB1 significantly inhibited cell malignant growth in vitro. Importantly, we showed that circSETDB1 was upregulated in serum exosomes in LUAD patients, and exosomal circSETDB1 levels were closely associated with disease stage. Finally, using RNA immunoprecipitation (RIP), bioinformatics, and luciferase reporter assays, we elucidated the implication of a circSETDB1/miR-7/specificity protein 1 (Sp1) axis in the development and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. |
format | Online Article Text |
id | pubmed-7875767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-78757672021-02-19 Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma Xu, Li Liao, Wei-Lin Lu, Qi-Jue Zhang, Peng Zhu, Ji Jiang, Ge-Ning Mol Ther Nucleic Acids Original Article Hypoxia is a common feature of solid tumors and has been associated with tumor aggressiveness and poor prognosis. Exosomes are involved in mediating cellular-environment interactions. Circular RNAs (circRNAs) are a class of non-coding RNA broadly found in cells and exosomes. However, the functions and regulatory mechanisms of exosomal circRNAs induced by hypoxia remain poorly understood in lung adenocarcinoma (LUAD) development. Differentially expressed circRNAs were identified between exosomes extracted from hypoxic and normoxic conditions through microarray analysis. We focused on hsa-circ-0003439 found on chromosome 1 and derived from SET domain bifurcated histone lysine methyltransferase 1 (SETDB1), and thus we named it circSETDB1. We discovered that exosomes obtained from hypoxic LUAD cells improved the migration, invasion, and proliferation capacity of normoxic LUAD cells. circSETDB1 was found to be significantly upregulated in hypoxia-induced exosomes from LUAD cell lines compared with exosomes in the normal condition. Moreover, knockdown of circSETDB1 significantly inhibited cell malignant growth in vitro. Importantly, we showed that circSETDB1 was upregulated in serum exosomes in LUAD patients, and exosomal circSETDB1 levels were closely associated with disease stage. Finally, using RNA immunoprecipitation (RIP), bioinformatics, and luciferase reporter assays, we elucidated the implication of a circSETDB1/miR-7/specificity protein 1 (Sp1) axis in the development and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. American Society of Gene & Cell Therapy 2021-01-26 /pmc/articles/PMC7875767/ /pubmed/33614250 http://dx.doi.org/10.1016/j.omtn.2021.01.019 Text en © 2021 The Author(s) 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 | Original Article Xu, Li Liao, Wei-Lin Lu, Qi-Jue Zhang, Peng Zhu, Ji Jiang, Ge-Ning Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma |
title | Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma |
title_full | Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma |
title_fullStr | Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma |
title_full_unstemmed | Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma |
title_short | Hypoxic tumor-derived exosomal circular RNA SETDB1 promotes invasive growth and EMT via the miR-7/Sp1 axis in lung adenocarcinoma |
title_sort | hypoxic tumor-derived exosomal circular rna setdb1 promotes invasive growth and emt via the mir-7/sp1 axis in lung adenocarcinoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875767/ https://www.ncbi.nlm.nih.gov/pubmed/33614250 http://dx.doi.org/10.1016/j.omtn.2021.01.019 |
work_keys_str_mv | AT xuli hypoxictumorderivedexosomalcircularrnasetdb1promotesinvasivegrowthandemtviathemir7sp1axisinlungadenocarcinoma AT liaoweilin hypoxictumorderivedexosomalcircularrnasetdb1promotesinvasivegrowthandemtviathemir7sp1axisinlungadenocarcinoma AT luqijue hypoxictumorderivedexosomalcircularrnasetdb1promotesinvasivegrowthandemtviathemir7sp1axisinlungadenocarcinoma AT zhangpeng hypoxictumorderivedexosomalcircularrnasetdb1promotesinvasivegrowthandemtviathemir7sp1axisinlungadenocarcinoma AT zhuji hypoxictumorderivedexosomalcircularrnasetdb1promotesinvasivegrowthandemtviathemir7sp1axisinlungadenocarcinoma AT jianggening hypoxictumorderivedexosomalcircularrnasetdb1promotesinvasivegrowthandemtviathemir7sp1axisinlungadenocarcinoma |