PMID- 27418134
OWN - NLM
STAT- MEDLINE
DCOM- 20180112
LR  - 20211204
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 32
DP  - 2016 Aug 9
TI  - MicroRNA-184 promotes differentiation of the retinal pigment epithelium by 
      targeting the AKT2/mTOR signaling pathway.
PG  - 52340-52353
LID - 10.18632/oncotarget.10566 [doi]
AB  - 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.
FAU - Jiang, Chao
AU  - Jiang C
AD  - Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical 
      University and State Key Laboratory of Reproductive Medicine, Nanjing Medical 
      University, Nanjing, China.
FAU - Qin, Bing
AU  - Qin B
AD  - Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical 
      University and State Key Laboratory of Reproductive Medicine, Nanjing Medical 
      University, Nanjing, China.
AD  - Department of Ophthalmology, The First People's Hospital of Suqian, Suqian, 
      China.
FAU - Liu, Guohua
AU  - Liu G
AD  - Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, 
      Shandong, China.
FAU - Sun, Xiantao
AU  - Sun X
AD  - Department of Ophthalmology, Children's Hospital of Zhengzhou, Zhengzhou, China.
FAU - Shi, Houxia
AU  - Shi H
AD  - Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical 
      University and State Key Laboratory of Reproductive Medicine, Nanjing Medical 
      University, Nanjing, China.
FAU - Ding, Sijia
AU  - Ding S
AD  - Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical 
      University and State Key Laboratory of Reproductive Medicine, Nanjing Medical 
      University, Nanjing, China.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Ophthalmology, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing, China.
FAU - Zhu, Meidong
AU  - Zhu M
AD  - Save Sight Institute, Discipline of Clinical Ophthalmology and Eye Health (CO9), 
      The University of Sydney, Sydney, Australia.
FAU - Chen, Xue
AU  - Chen X
AD  - Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical 
      University and State Key Laboratory of Reproductive Medicine, Nanjing Medical 
      University, Nanjing, China.
FAU - Zhao, Chen
AU  - Zhao C
AD  - Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical 
      University and State Key Laboratory of Reproductive Medicine, Nanjing Medical 
      University, Nanjing, China.
AD  - Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, 
      China.
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat Sen 
      University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (MIRN184 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT2 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Cell Dedifferentiation/*physiology
MH  - Cell Differentiation/physiology
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - Induced Pluripotent Stem Cells/cytology/*metabolism
MH  - Macular Degeneration/*metabolism
MH  - Male
MH  - MicroRNAs/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Retinal Pigment Epithelium/cytology/*metabolism
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Zebrafish
PMC - PMC5239556
OTO - NOTNLM
OT  - AKT2
OT  - differentiation
OT  - mTOR
OT  - miR-184
OT  - retinal pigment epithelium
COIS- None
EDAT- 2016/07/16 06:00
MHDA- 2018/01/13 06:00
PMCR- 2016/08/09
CRDT- 2016/07/16 06:00
PHST- 2016/02/14 00:00 [received]
PHST- 2016/06/30 00:00 [accepted]
PHST- 2016/07/16 06:00 [pubmed]
PHST- 2018/01/13 06:00 [medline]
PHST- 2016/07/16 06:00 [entrez]
PHST- 2016/08/09 00:00 [pmc-release]
AID - 10566 [pii]
AID - 10.18632/oncotarget.10566 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Aug 9;7(32):52340-52353. doi: 10.18632/oncotarget.10566.