PUBLICATION
MicroRNA-184 promotes differentiation of the retinal pigment epithelium by targeting the AKT2/mTOR signaling pathway
- Authors
- Jiang, C., Qin, B., Liu, G., Sun, X., Shi, H., Ding, S., Liu, Y., Zhu, M., Chen, X., Zhao, C.
- ID
- ZDB-PUB-160716-7
- Date
- 2016
- Source
- Oncotarget 7(32): 52340-52353 (Journal)
- Registered Authors
- Keywords
- AKT2, differentiation, mTOR, miR-184, retinal pigment epithelium
- MeSH Terms
-
- Animals
- Female
- Gene Expression Regulation
- Induced Pluripotent Stem Cells/cytology
- Induced Pluripotent Stem Cells/metabolism*
- Aged
- Zebrafish
- Retinal Pigment Epithelium/cytology
- Retinal Pigment Epithelium/metabolism*
- Signal Transduction/physiology
- Cell Dedifferentiation/physiology*
- Male
- Macular Degeneration/metabolism*
- MicroRNAs/metabolism*
- Humans
- Cell Differentiation/physiology
- Proto-Oncogene Proteins c-akt/metabolism
- Adult
- TOR Serine-Threonine Kinases/metabolism
- PubMed
- 27418134 Full text @ Oncotarget
Citation
Jiang, C., Qin, B., Liu, G., Sun, X., Shi, H., Ding, S., Liu, Y., Zhu, M., Chen, X., Zhao, C. (2016) MicroRNA-184 promotes differentiation of the retinal pigment epithelium by targeting the AKT2/mTOR signaling pathway. Oncotarget. 7(32):52340-52353.
Abstract
Dedifferentiation of retinal pigment epithelium (RPE) cells is a crucial contributing factor to the pathology of retinal degenerative diseases, including age-related macular degeneration (AMD). Herein, we aim to reveal the roles of microRNAs (miRNAs) in RPE dedifferentiation and seek for potential therapeutic targets. Based on the microarray data, miR-184 was sorted out as the most up-regulated signature along with the differentiation from human induced pluripotent stem cells (hiPSC) to RPE cells, suggesting its potential promotive role in RPE differentiation. In vitro study indicated that miR-184 insufficiency suppressed RPE differentiation, typified by reduction of RPE markers, and promoted cell proliferation and migration. The role of miR-184 in maintaining regular RPE function was further proved in zebrafish studies. We also noticed that miR-184 expression was reduced in the macular RPE-choroid from a donor with RPE dysfunction compared to a healthy control. We next demonstrated that RAC-beta serine/threonine-protein kinase (AKT2) was a direct target for miR-184. MiR-184 promoted RPE differentiation via suppression of AKT2/mammalian target of rapamycin (mTOR) signaling pathway. We also found that AKT2 was up-regulated in macular RPE-choroid of the donor with RPE dysfunction and dry AMD patients. Taken together, our findings suggest that miR-184 insufficiency is involved in the pathogenesis of dry AMD. MiR-184 promotes RPE differentiation via inhibiting the AKT2/mTOR signaling pathway. MiR-184 based supplementary therapeutics and mTOR blocker, like rapamycin, are prospective options for AMD treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping