Cargando…

Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas

BACKGROUND: Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the...

Descripción completa

Detalles Bibliográficos
Autores principales: He, Jiehua, Huang, Zuoyu, He, Mingliang, Liao, Jianyou, Zhang, Qianqian, Wang, Shengwen, Xie, Lin, Ouyang, Leping, Koeffler, H. Phillip, Yin, Dong, Liu, Anmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986105/
https://www.ncbi.nlm.nih.gov/pubmed/31992303
http://dx.doi.org/10.1186/s12943-019-1120-1
_version_ 1783491917248462848
author He, Jiehua
Huang, Zuoyu
He, Mingliang
Liao, Jianyou
Zhang, Qianqian
Wang, Shengwen
Xie, Lin
Ouyang, Leping
Koeffler, H. Phillip
Yin, Dong
Liu, Anmin
author_facet He, Jiehua
Huang, Zuoyu
He, Mingliang
Liao, Jianyou
Zhang, Qianqian
Wang, Shengwen
Xie, Lin
Ouyang, Leping
Koeffler, H. Phillip
Yin, Dong
Liu, Anmin
author_sort He, Jiehua
collection PubMed
description BACKGROUND: Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS. METHODS: A bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural development. Quantitative real-time PCR was used to detect the expression of circ-MAPK4 and target miRNAs. Glioma cells were transfected with circ-MAPK4 siRNAs, then cell proliferation, apoptosis, transwell assays, as well as tumorigenesis and TUNEL assays, were performed to examine effect of circ-MAPK4 in vitro and vivo. Biotinylated-circ-MAPK4 probe based pull-down assay was conducted to confirm the relationship between circ-MAPK4 and miR-125-3p. RESULTS: In this study, we identified a circRNA, circ-MAPK4 (has_circ_0047688), which was downregulated during early neural differentiation. In gliomas, circ-MAPK4 acted as an oncogene, was inversely upregulated and linked to clinical pathological stage of gliomas (P < 0.05). Next, we verified that circ-MAPK4 promoted the survival and inhibited the apoptosis of glioma cells in vitro and in vivo. Furthermore, we proved that circ-MAPK4 was involved in regulating p38/MAPK pathway, which affected glioma proliferation and apoptosis. Finally, miR-125a-3p, a miRNA exhibited tumor-suppressive function through impairing p38/MAPK pathway, which was increased by inhibiting circ-MAPK4 and could be pulled down by circ-MAPK4. Inhibition of miR-125a-3p could partly rescue the increased phosphorylation levels of p38/MAPK and the elevated amount of apoptosis inducing by knockdown of circ-MAPK4. CONCLUSIONS: Our findings suggest that circ-MAPK4 is a critical player in glioma cell survival and apoptosis via p38/MAPK signaling pathway through modulation of miR-125a-3p, which can serve as a new therapeutic target for treatment of gliomas.
format Online
Article
Text
id pubmed-6986105
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-69861052020-01-30 Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas He, Jiehua Huang, Zuoyu He, Mingliang Liao, Jianyou Zhang, Qianqian Wang, Shengwen Xie, Lin Ouyang, Leping Koeffler, H. Phillip Yin, Dong Liu, Anmin Mol Cancer Research BACKGROUND: Recent evidences have shown that circular RNAs (circRNAs) are frequently dysregulated and play paramount roles in various cancers. circRNAs are abundant in central nervous system (CNS); however, few studies describe the clinical significance and role of circRNAs in gliomas, which is the most common and aggressive primary malignant tumor in the CNS. METHODS: A bioinformatics analysis was performed to profile and screen the dyregulated circRNAs during early neural development. Quantitative real-time PCR was used to detect the expression of circ-MAPK4 and target miRNAs. Glioma cells were transfected with circ-MAPK4 siRNAs, then cell proliferation, apoptosis, transwell assays, as well as tumorigenesis and TUNEL assays, were performed to examine effect of circ-MAPK4 in vitro and vivo. Biotinylated-circ-MAPK4 probe based pull-down assay was conducted to confirm the relationship between circ-MAPK4 and miR-125-3p. RESULTS: In this study, we identified a circRNA, circ-MAPK4 (has_circ_0047688), which was downregulated during early neural differentiation. In gliomas, circ-MAPK4 acted as an oncogene, was inversely upregulated and linked to clinical pathological stage of gliomas (P < 0.05). Next, we verified that circ-MAPK4 promoted the survival and inhibited the apoptosis of glioma cells in vitro and in vivo. Furthermore, we proved that circ-MAPK4 was involved in regulating p38/MAPK pathway, which affected glioma proliferation and apoptosis. Finally, miR-125a-3p, a miRNA exhibited tumor-suppressive function through impairing p38/MAPK pathway, which was increased by inhibiting circ-MAPK4 and could be pulled down by circ-MAPK4. Inhibition of miR-125a-3p could partly rescue the increased phosphorylation levels of p38/MAPK and the elevated amount of apoptosis inducing by knockdown of circ-MAPK4. CONCLUSIONS: Our findings suggest that circ-MAPK4 is a critical player in glioma cell survival and apoptosis via p38/MAPK signaling pathway through modulation of miR-125a-3p, which can serve as a new therapeutic target for treatment of gliomas. BioMed Central 2020-01-28 /pmc/articles/PMC6986105/ /pubmed/31992303 http://dx.doi.org/10.1186/s12943-019-1120-1 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
He, Jiehua
Huang, Zuoyu
He, Mingliang
Liao, Jianyou
Zhang, Qianqian
Wang, Shengwen
Xie, Lin
Ouyang, Leping
Koeffler, H. Phillip
Yin, Dong
Liu, Anmin
Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas
title Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas
title_full Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas
title_fullStr Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas
title_full_unstemmed Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas
title_short Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas
title_sort circular rna mapk4 (circ-mapk4) inhibits cell apoptosis via mapk signaling pathway by sponging mir-125a-3p in gliomas
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986105/
https://www.ncbi.nlm.nih.gov/pubmed/31992303
http://dx.doi.org/10.1186/s12943-019-1120-1
work_keys_str_mv AT hejiehua circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT huangzuoyu circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT hemingliang circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT liaojianyou circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT zhangqianqian circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT wangshengwen circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT xielin circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT ouyangleping circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT koefflerhphillip circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT yindong circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas
AT liuanmin circularrnamapk4circmapk4inhibitscellapoptosisviamapksignalingpathwaybyspongingmir125a3pingliomas