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Exp Eye Res. 2019 Jul;184:278-285. doi: 10.1016/j.exer.2019.03.017. Epub 2019 Mar 24.

Reduction of circular RNA expression associated with human retinoblastoma.

Author information

1
Department of Ophthalmology, Xinhua Hospital, Medical School, Shanghai Jiao Tong University, 1665 Kong Jiang Road, Shanghai, 200092, China.
2
Shanghai Medical College, Fudan University, 131 Dong'An Road, Shanghai, 200032, China.
3
Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong'An Road, Shanghai, 200032, China.
4
Department of Ophthalmology, Xinhua Hospital, Medical School, Shanghai Jiao Tong University, 1665 Kong Jiang Road, Shanghai, 200092, China. Electronic address: jixunda@xinhuamed.com.cn.
5
Department of Ophthalmology, Xinhua Hospital, Medical School, Shanghai Jiao Tong University, 1665 Kong Jiang Road, Shanghai, 200092, China. Electronic address: zhaopeiquan@xinhuamed.com.cn.

Abstract

This study investigated the profile of circular RNA (circRNA) expression and its epigenetic role associated with human retinoblastoma (RB). Twelve paired primary samples from un-treated RB patients (primary RB samples and corresponding adjacent normal retinal samples) and eight recurrent RB samples from RB patients having recurrence after treatment were collected. Ribosomal-RNA depleted sequencing was performed in four paired primary samples. Quantitative polymerase chain reaction was conducted to validate circRNA and mRNA expression in the other eight paired primary samples and in eight recurrent RB samples. Bioinformatic analysis was applied to predict the oncological signal pathways and the binding microRNA (miRNA) of circRNA. As a result, a total of 47640 circRNAs were identified by RNA-sequencing, with a lower abundance of circRNAs in primary RB samples relative to matched normal retinal samples [22366 (47%) versus 37161 (78%), P <0.001]. Among the 11887 overlapping circRNAs in both RB and normal retinal samples, 550 circRNAs were downregulated and seven were upregulated in primary RB samples compared to normal retinal samples. The host genes of the differentially expressed circRNAs were associated with chromatin modification. TET1-has_circ_0093996 (ten-eleven translocation-1), whose host gene TET1 participates in chromatin modifying, was downregulated in both primary and recurrent RB samples. Programmed cell death 4 (PDCD4) was also downregulated in both primary and recurrent RB samples. We used bioinformatic tools to construct a complete regulatory axis including TET1-has_circ_0093996-miR-183-PDCD4 that regulates RB pathogenesis. In conclusion, circRNA expression is downregulated in RB tumor, which suggests epigenetic regulation of RB pathogenesis by circRNAs.

PMID:
30917906
DOI:
10.1016/j.exer.2019.03.017

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