Cargando…

Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells

Uncontrolled retinal pigment epithelial (RPE) cell proliferation/migration contribute to the pathological tractional membrane development in proliferative vitreoretinopathy. Recent studies reported that microRNA (miR)-124 controls various cellular functions via the direct targeting of small Ras homo...

Descripción completa

Detalles Bibliográficos
Autores principales: Jun, Jong Hwa, Son, Myeong-Jin, Lee, Hyun-Gyo, Shim, Kyu Young, Baek, Won-Ki, Kim, Jae-Young, Joo, Choun-Ki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508981/
https://www.ncbi.nlm.nih.gov/pubmed/32963317
http://dx.doi.org/10.1038/s41598-020-72360-5
_version_ 1783585507230351360
author Jun, Jong Hwa
Son, Myeong-Jin
Lee, Hyun-Gyo
Shim, Kyu Young
Baek, Won-Ki
Kim, Jae-Young
Joo, Choun-Ki
author_facet Jun, Jong Hwa
Son, Myeong-Jin
Lee, Hyun-Gyo
Shim, Kyu Young
Baek, Won-Ki
Kim, Jae-Young
Joo, Choun-Ki
author_sort Jun, Jong Hwa
collection PubMed
description Uncontrolled retinal pigment epithelial (RPE) cell proliferation/migration contribute to the pathological tractional membrane development in proliferative vitreoretinopathy. Recent studies reported that microRNA (miR)-124 controls various cellular functions via the direct targeting of small Ras homolog family member G (RHOG). Therefore, we investigated the role of the neuron-specific miR-124 and RHOG in RPE cell proliferation/migration. Alterations in miR-124 and RhoG expression, as per cell confluence were evaluated through quantitative real-time PCR and western blotting, respectively. After transfection with miR-124, we quantified RPE cell viability and migration and observed cell polarization and lamellipodia protrusions. We evaluated the expression of RHOG/RAC1 pathway molecules in miR-124-transfected RPE cells. Endogenous miR-124 expression increased proportionally to RPE cell density, but decreased after 100% confluence. Overexpression of miR-124 decreased cell viability and migration, BrdU incorporation, and Ki-67 expression. Inhibition of endogenous miR-124 expression promoted RPE cell migration. Transfection with miR-124 reduced cell polarization, lamellipodia protrusion, and RHOG mRNA 3′ untranslated region luciferase activity. Like miR-124 overexpression, RhoG knockdown decreased RPE cell viability, wound healing, and migration, and altered the expression of cell cycle regulators. These results suggest that miR-124 could be a therapeutic target to alleviate fibrovascular proliferation in retinal diseases by regulating RPE proliferation/migration via RHOG.
format Online
Article
Text
id pubmed-7508981
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-75089812020-09-24 Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells Jun, Jong Hwa Son, Myeong-Jin Lee, Hyun-Gyo Shim, Kyu Young Baek, Won-Ki Kim, Jae-Young Joo, Choun-Ki Sci Rep Article Uncontrolled retinal pigment epithelial (RPE) cell proliferation/migration contribute to the pathological tractional membrane development in proliferative vitreoretinopathy. Recent studies reported that microRNA (miR)-124 controls various cellular functions via the direct targeting of small Ras homolog family member G (RHOG). Therefore, we investigated the role of the neuron-specific miR-124 and RHOG in RPE cell proliferation/migration. Alterations in miR-124 and RhoG expression, as per cell confluence were evaluated through quantitative real-time PCR and western blotting, respectively. After transfection with miR-124, we quantified RPE cell viability and migration and observed cell polarization and lamellipodia protrusions. We evaluated the expression of RHOG/RAC1 pathway molecules in miR-124-transfected RPE cells. Endogenous miR-124 expression increased proportionally to RPE cell density, but decreased after 100% confluence. Overexpression of miR-124 decreased cell viability and migration, BrdU incorporation, and Ki-67 expression. Inhibition of endogenous miR-124 expression promoted RPE cell migration. Transfection with miR-124 reduced cell polarization, lamellipodia protrusion, and RHOG mRNA 3′ untranslated region luciferase activity. Like miR-124 overexpression, RhoG knockdown decreased RPE cell viability, wound healing, and migration, and altered the expression of cell cycle regulators. These results suggest that miR-124 could be a therapeutic target to alleviate fibrovascular proliferation in retinal diseases by regulating RPE proliferation/migration via RHOG. Nature Publishing Group UK 2020-09-22 /pmc/articles/PMC7508981/ /pubmed/32963317 http://dx.doi.org/10.1038/s41598-020-72360-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jun, Jong Hwa
Son, Myeong-Jin
Lee, Hyun-Gyo
Shim, Kyu Young
Baek, Won-Ki
Kim, Jae-Young
Joo, Choun-Ki
Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells
title Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells
title_full Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells
title_fullStr Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells
title_full_unstemmed Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells
title_short Regulation of Ras homolog family member G by microRNA-124 regulates proliferation and migration of human retinal pigment epithelial cells
title_sort regulation of ras homolog family member g by microrna-124 regulates proliferation and migration of human retinal pigment epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508981/
https://www.ncbi.nlm.nih.gov/pubmed/32963317
http://dx.doi.org/10.1038/s41598-020-72360-5
work_keys_str_mv AT junjonghwa regulationofrashomologfamilymembergbymicrorna124regulatesproliferationandmigrationofhumanretinalpigmentepithelialcells
AT sonmyeongjin regulationofrashomologfamilymembergbymicrorna124regulatesproliferationandmigrationofhumanretinalpigmentepithelialcells
AT leehyungyo regulationofrashomologfamilymembergbymicrorna124regulatesproliferationandmigrationofhumanretinalpigmentepithelialcells
AT shimkyuyoung regulationofrashomologfamilymembergbymicrorna124regulatesproliferationandmigrationofhumanretinalpigmentepithelialcells
AT baekwonki regulationofrashomologfamilymembergbymicrorna124regulatesproliferationandmigrationofhumanretinalpigmentepithelialcells
AT kimjaeyoung regulationofrashomologfamilymembergbymicrorna124regulatesproliferationandmigrationofhumanretinalpigmentepithelialcells
AT joochounki regulationofrashomologfamilymembergbymicrorna124regulatesproliferationandmigrationofhumanretinalpigmentepithelialcells