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miR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration.
FEBS J. 2014 Dec; 281(23):5251-64.FJ

Abstract

MicroRNA 184 (miR-184) is known to play a key role in neurological development and apoptosis and is highly expressed in mouse brain, mouse corneal epithelium, zebrafish lens and human retinal pigment epithelium (RPE). However, the role of miR-184 in RPE is largely unknown. We investigated the role of miR-184 in RPE and its possible implication in age-related macular degeneration (AMD). Proteomic analysis identified the ezrin (EZR) gene as a target of miR-184 in human RPE. EZR is a membrane cytoskeleton crosslinker that is also known to bind to lysosomal-associated membrane protein 1 (LAMP-1) during the formation of phagocytic vacuoles. In adult retinal pigment epithelium 19 (ARPE19) cells, inhibition of miR-184 resulted in upregulation of EZR mRNA and EZR protein, and induced downregulation of LAMP-1. The inhibition of miR-184 decreased EZR-bound LAMP-1 protein levels and affected phagocytic activity in ARPE19 cells. In primary culture of human RPE isolated from eyes of AMD donors (AMD RPE), miR-184 was significantly downregulated compared with control (normal) RPE. Downregulation of miR-184 was consistent with significantly lower levels of LAMP-1 protein in AMD RPE, and overexpression of MIR-184 in AMD RPE was able to rescue LAMP-1 protein expression to normal levels. Altogether, these observations suggest a novel role for miR-184 in RPE health and support a model proposing that downregulation of miR-184 expression during aging may result in dysregulation of RPE function, contributing to retinal degeneration.

Authors+Show Affiliations

Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25251993

Citation

Murad, Najiba, et al. "MiR-184 Regulates Ezrin, LAMP-1 Expression, Affects Phagocytosis in Human Retinal Pigment Epithelium and Is Downregulated in Age-related Macular Degeneration." The FEBS Journal, vol. 281, no. 23, 2014, pp. 5251-64.
Murad N, Kokkinaki M, Gunawardena N, et al. MiR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration. FEBS J. 2014;281(23):5251-64.
Murad, N., Kokkinaki, M., Gunawardena, N., Gunawan, M. S., Hathout, Y., Janczura, K. J., Theos, A. C., & Golestaneh, N. (2014). MiR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration. The FEBS Journal, 281(23), 5251-64. https://doi.org/10.1111/febs.13066
Murad N, et al. MiR-184 Regulates Ezrin, LAMP-1 Expression, Affects Phagocytosis in Human Retinal Pigment Epithelium and Is Downregulated in Age-related Macular Degeneration. FEBS J. 2014;281(23):5251-64. PubMed PMID: 25251993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-184 regulates ezrin, LAMP-1 expression, affects phagocytosis in human retinal pigment epithelium and is downregulated in age-related macular degeneration. AU - Murad,Najiba, AU - Kokkinaki,Maria, AU - Gunawardena,Nishantha, AU - Gunawan,Mia S, AU - Hathout,Yetrib, AU - Janczura,Karolina J, AU - Theos,Alexander C, AU - Golestaneh,Nady, Y1 - 2014/10/13/ PY - 2013/11/22/received PY - 2014/09/15/revised PY - 2014/09/19/accepted PY - 2014/9/25/entrez PY - 2014/9/25/pubmed PY - 2015/1/27/medline KW - AMD KW - LAMP-1 KW - RPE KW - ezrin KW - miR-184 SP - 5251 EP - 64 JF - The FEBS journal JO - FEBS J VL - 281 IS - 23 N2 - MicroRNA 184 (miR-184) is known to play a key role in neurological development and apoptosis and is highly expressed in mouse brain, mouse corneal epithelium, zebrafish lens and human retinal pigment epithelium (RPE). However, the role of miR-184 in RPE is largely unknown. We investigated the role of miR-184 in RPE and its possible implication in age-related macular degeneration (AMD). Proteomic analysis identified the ezrin (EZR) gene as a target of miR-184 in human RPE. EZR is a membrane cytoskeleton crosslinker that is also known to bind to lysosomal-associated membrane protein 1 (LAMP-1) during the formation of phagocytic vacuoles. In adult retinal pigment epithelium 19 (ARPE19) cells, inhibition of miR-184 resulted in upregulation of EZR mRNA and EZR protein, and induced downregulation of LAMP-1. The inhibition of miR-184 decreased EZR-bound LAMP-1 protein levels and affected phagocytic activity in ARPE19 cells. In primary culture of human RPE isolated from eyes of AMD donors (AMD RPE), miR-184 was significantly downregulated compared with control (normal) RPE. Downregulation of miR-184 was consistent with significantly lower levels of LAMP-1 protein in AMD RPE, and overexpression of MIR-184 in AMD RPE was able to rescue LAMP-1 protein expression to normal levels. Altogether, these observations suggest a novel role for miR-184 in RPE health and support a model proposing that downregulation of miR-184 expression during aging may result in dysregulation of RPE function, contributing to retinal degeneration. SN - 1742-4658 UR - https://www.unboundmedicine.com/medline/citation/25251993/miR_184_regulates_ezrin_LAMP_1_expression_affects_phagocytosis_in_human_retinal_pigment_epithelium_and_is_downregulated_in_age_related_macular_degeneration_ L2 - https://doi.org/10.1111/febs.13066 DB - PRIME DP - Unbound Medicine ER -