Oncotarget

Research Papers:

miR-29a regulates the proliferation and differentiation of retinal progenitors by targeting Rbm8a

Yi Zhang, Bingqiao Shen, Dandan Zhang, Yuyao Wang, Zhimin Tang, Ni Ni, Xiaoliang Jin, Min Luo, Hao Sun and Ping Gu _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:31993-32008. https://doi.org/10.18632/oncotarget.16669

Metrics: PDF 832 views  |   HTML 1614 views  |   ?  


Abstract

Yi Zhang1,*, Bingqiao Shen1,*, Dandan Zhang1,*, Yuyao Wang1, Zhimin Tang1, Ni Ni1, Xiaoliang Jin1, Min Luo1, Hao Sun1, Ping Gu1

1Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China

*These authors contributed equally to this work

Correspondence to:

Min Luo, email: qiangson@sh163.net

Hao Sun, email: sunhao6666@126.com

Ping Gu, email: guping2009@126.com

Keywords: retinal progenitor cells, microRNA (miR)-29a, RBM8A, proliferation, differentiation

Received: December 02, 2016     Accepted: March 17, 2017     Published: March 29, 2017

ABSTRACT

During development, tight regulation of the expansion of retinal progenitor cells (RPCs) and their differentiation into neuronal and glial cells is important for retinal formation and function. Our study demonstrated that microRNA (miR)-29a modulated the proliferation and differentiation of RPCs by suppressing RBM8A (one of the factors in the exon junction complex). Particularly, overexpression of miR-29a reduced RPC proliferation but accelerated RPC differentiation. By contrast, reduction of endogenous miR-29a elicited the opposite effects. Overexpression of miR-29a repressed the translation of Rbm8a, thus negatively regulating RPC proliferation and promoting the neuronal and glial differentiation of RPCs, and knockdown of endogenous Rbm8a phenocopied the observed effects of miR-29a overexpression. Furthermore, a luciferase reporter assay showed that miR-29a directly interacted with the Rbm8a mRNA 3′UTR, which indicated that Rbm8a is the direct target of miR-29a. To further verify the result, co-overexpression of the Rbm8a 3′ UTR-wt (plasmids into which the Rbm8a 3′ UTR sequence had been introduced) and miR-29a in RPCs rescued the phenotype associated with miR-29a overexpression, reversing the promotion of differentiation and inhibition of proliferation. These results show a novel mechanism by which miR-29a regulates the proliferation and differentiation of RPCs through Rbm8a.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 16669