Cargando…
Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway
Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighte...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859531/ https://www.ncbi.nlm.nih.gov/pubmed/33553184 http://dx.doi.org/10.3389/fcell.2021.626027 |
_version_ | 1783646755334651904 |
---|---|
author | Lv, Wenchang Liu, Shengxuan Zhang, Qi Hu, Weijie Wu, Yiping Ren, Yuping |
author_facet | Lv, Wenchang Liu, Shengxuan Zhang, Qi Hu, Weijie Wu, Yiping Ren, Yuping |
author_sort | Lv, Wenchang |
collection | PubMed |
description | Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighted the roles of circRNAs in acting as miRNA sponges. However, up to date, the regulatory mechanism of circRNAs in the pathological process of keloids has rarely been reported. In this study, cell proliferation, cell migration, flow cytometry, western blotting, fluorescence in situ hybridization, dual-luciferase activity, and immunohistochemistry assays were applied to explore the roles and mechanisms of the circCOL5A1/miR-7-5p/Epac1 axis in the keloid. The therapeutic potential of circCOL5A1 was investigated by establishing keloid implantation models. The RT-qPCR result revealed that circCOL5A1 expression was obviously higher in keloid tissues and keloid fibroblasts. Subsequent cellular experiments demonstrated that circCOL5A1 knockdown repressed the proliferation, migration, extracellular matrix (ECM) deposition, whereas promoted cell apoptosis, through the PI3K/Akt signaling pathway. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that both circCOL5A1 and miR-7-5p were located in the cytoplasm. The luciferase reporter gene assay confirmed that exact binding sites were present between circCOL5A1 and miR-7-5p, as well as between miR-7-5p and Epac1. Collectively, the present study revealed that circCOL5A1 functioned as competing endogenous RNA (ceRNA) by adsorbing miR-7-5p to release Epac1, which contributed to pathological hyperplasia of keloids through activating the PI3K/Akt signaling pathway. Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids. |
format | Online Article Text |
id | pubmed-7859531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78595312021-02-05 Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway Lv, Wenchang Liu, Shengxuan Zhang, Qi Hu, Weijie Wu, Yiping Ren, Yuping Front Cell Dev Biol Cell and Developmental Biology Keloids, as a result of abnormal wound healing in susceptible individuals, are characterized by the hyper-proliferation of fibroblasts and exaggerated deposition of extracellular matrix. Current surgical and therapeutic modalities provide limited satisfactory results. Growing evidence has highlighted the roles of circRNAs in acting as miRNA sponges. However, up to date, the regulatory mechanism of circRNAs in the pathological process of keloids has rarely been reported. In this study, cell proliferation, cell migration, flow cytometry, western blotting, fluorescence in situ hybridization, dual-luciferase activity, and immunohistochemistry assays were applied to explore the roles and mechanisms of the circCOL5A1/miR-7-5p/Epac1 axis in the keloid. The therapeutic potential of circCOL5A1 was investigated by establishing keloid implantation models. The RT-qPCR result revealed that circCOL5A1 expression was obviously higher in keloid tissues and keloid fibroblasts. Subsequent cellular experiments demonstrated that circCOL5A1 knockdown repressed the proliferation, migration, extracellular matrix (ECM) deposition, whereas promoted cell apoptosis, through the PI3K/Akt signaling pathway. Furthermore, RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that both circCOL5A1 and miR-7-5p were located in the cytoplasm. The luciferase reporter gene assay confirmed that exact binding sites were present between circCOL5A1 and miR-7-5p, as well as between miR-7-5p and Epac1. Collectively, the present study revealed that circCOL5A1 functioned as competing endogenous RNA (ceRNA) by adsorbing miR-7-5p to release Epac1, which contributed to pathological hyperplasia of keloids through activating the PI3K/Akt signaling pathway. Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids. Frontiers Media S.A. 2021-01-21 /pmc/articles/PMC7859531/ /pubmed/33553184 http://dx.doi.org/10.3389/fcell.2021.626027 Text en Copyright © 2021 Lv, Liu, Zhang, Hu, Wu and Ren. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Lv, Wenchang Liu, Shengxuan Zhang, Qi Hu, Weijie Wu, Yiping Ren, Yuping Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway |
title | Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway |
title_full | Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway |
title_fullStr | Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway |
title_full_unstemmed | Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway |
title_short | Circular RNA CircCOL5A1 Sponges the MiR-7-5p/Epac1 Axis to Promote the Progression of Keloids Through Regulating PI3K/Akt Signaling Pathway |
title_sort | circular rna circcol5a1 sponges the mir-7-5p/epac1 axis to promote the progression of keloids through regulating pi3k/akt signaling pathway |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859531/ https://www.ncbi.nlm.nih.gov/pubmed/33553184 http://dx.doi.org/10.3389/fcell.2021.626027 |
work_keys_str_mv | AT lvwenchang circularrnacirccol5a1spongesthemir75pepac1axistopromotetheprogressionofkeloidsthroughregulatingpi3kaktsignalingpathway AT liushengxuan circularrnacirccol5a1spongesthemir75pepac1axistopromotetheprogressionofkeloidsthroughregulatingpi3kaktsignalingpathway AT zhangqi circularrnacirccol5a1spongesthemir75pepac1axistopromotetheprogressionofkeloidsthroughregulatingpi3kaktsignalingpathway AT huweijie circularrnacirccol5a1spongesthemir75pepac1axistopromotetheprogressionofkeloidsthroughregulatingpi3kaktsignalingpathway AT wuyiping circularrnacirccol5a1spongesthemir75pepac1axistopromotetheprogressionofkeloidsthroughregulatingpi3kaktsignalingpathway AT renyuping circularrnacirccol5a1spongesthemir75pepac1axistopromotetheprogressionofkeloidsthroughregulatingpi3kaktsignalingpathway |