由于E50K OPTN突变导致的miR-9表达降低会引起BDNF表达紊乱，进而导致RGC-5细胞凋亡。

Decreased expression of miR‑9 due to E50K OPTN mutation causes disruption of the expression of BDNF leading to RGC‑5 cell apoptosis.

作者信息

Jiang Bo, Gao Lin, Lei Dawei, Liu Jiannan, Shao Zhengbo, Zhou Xinrong, Li Renke, Wu Donglai, Xue Fei, Zhu Yuanmao, Yuan Huiping

机构信息

Department of Ophthalmology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

Division of Cardiovascular Surgery and Toronto General Research Institute, University Health Network and Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, ON M5G 1L7, Canada.

出版信息

Mol Med Rep. 2016 Nov;14(5):4901-4905. doi: 10.3892/mmr.2016.5810. Epub 2016 Oct 6.

DOI:10.3892/mmr.2016.5810

PMID:27748809

Abstract

The aims of the present study were to investigate the effect of E50K optineurin (OPTN) mutation on RGC‑5 cells and to define the role of microRNA‑9 (miR‑9) in this system. Transfected RGC‑5 cells were used to evaluate the effects of E50K OPTN on the expression of miR‑9 and subsequent disruption of RGC‑5 cell apoptosis was analyzed using western blotting. The results showed that the expression of E50K OPTN was associated with a marked reduction in the levels of miR‑9 in the E50K OPTN‑transfected RGC‑5 cells. The E50K OPTN‑dependent reductions in miR‑9 led to increased expression of the transcriptional repressor, RE1‑silencing transcription factor and decreased the expression of brain‑derived neurotrophic factor. Thus, E50K OPTN may disrupt the expression of miR‑9, suggesting a potential mechanism by which E50K OPTN mutation may lead to RGC‑5 cell apoptosis.

摘要

本研究的目的是探讨E50K视神经病相关蛋白（OPTN）突变对RGC-5细胞的影响，并确定微小RNA-9（miR-9）在该系统中的作用。使用转染的RGC-5细胞来评估E50K OPTN对miR-9表达的影响，并通过蛋白质印迹法分析随后RGC-5细胞凋亡的破坏情况。结果显示，在转染E50K OPTN的RGC-5细胞中，E50K OPTN的表达与miR-9水平的显著降低相关。E50K OPTN导致的miR-9减少导致转录抑制因子RE1沉默转录因子的表达增加，并降低了脑源性神经营养因子的表达。因此，E50K OPTN可能会破坏miR-9的表达，提示E50K OPTN突变可能导致RGC-5细胞凋亡的潜在机制。