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lncRNA MEG3, Acting as a ceRNA, Modulates RPE Differentiation Through the miR-7-5p/Pax6 Axis

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A Correction to this article was published on 01 June 2021

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Abstract

Accumulated evidence indicated that long non-coding RNAs (lncRNAs) involves in numerous biological and pathological processes, including age-related macular degeneration (AMD). Dysfunction and dedifferentiation of retinal pigment epithelium (RPE) cells have been demonstrated to be one of the crucial factor in AMD etiology. Herein, we aim to investigate the essential role of lncRNA maternally expressed gene 3 (MEG3) in AMD progression. Expression patterns of MEG3 were measured in dysfunctional REP cells exposed with H2O2 or TNF-α using qRT-PCR assay. Specifically, the intercellular distribution of MEG3 in REP cells was further explored using the subcellular fraction detection. Relative expression of RPE markers or RPE dedifferentiation-related markers was determined using qRT-PCR and western blot analysis, respectively. Immunofluorescence staining was performed to examine the expressions of RPE markers ZO-1 and β-catenin. Concentration of vascular endothelial growth factor (VEGFA) in the supernatant was detected using ELISA kit. Luciferase reporter assay was performed to verify the MEG3/miR-7-5p/Pax6 regulatory network, which was further determined in in vitro studies. MEG3 expression was significantly decreased in H2O2 or TNF-α-treated REP cells, and it was upregulated along with RPE differentiation. Reduced MEG3 expression resulted in RPE dedifferentiation, which was indicated by decreased expressions of RPE markers, accumulated mitochondrial reactive oxygen species, and reduced VEGFA. Mechanistically, MEG3 functioned as a sponge for miR-7-5p to restore the expression of Pax6. Our study demonstrated that MEG3 exerts a protective role against AMD by maintaining RPE differentiation via miR-7-5p/Pax6 axis, suggesting a protective therapeutic target in AMD treatment.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Change history

Abbreviations

AMD:

Age-related macular degeneration

ceRNA:

Endogenous RNA

hiPSCs:

Human-induced pluripotent stem cells

lncRNAs:

Long non-coding RNAs

miRNA:

Micro RNA

PCR:

Quantitative real-time polymerase chain reaction

RPE:

Retinal pigment epithelium

ROS:

Reactive oxygen species

siRNA:

Small interfering RNA

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Funding

This work was supported by Zhejiang Provincial Medical and Health Science and Technology Project (Nos. 2020KY150, 2020KY528, 2020KY578, 2021KY128) and Zhejiang Provincial Science and Technology Program of Traditional Chinese Medicine (No. 2019ZA072).

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Author notes

  1. Hong-Jing Sun and Fang-Fang Zhang are first co-authors.

Authors and Affiliations

  1. Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, Zhejiang, People’s Republic of China

    Hong-Jing Sun, Qing Xiao & Jia Xu

  2. School of Public Health, Hangzhou Medical College, No. 182, Tianmushan Road, Hangzhou, 310013, Zhejiang, People’s Republic of China

    Fang-Fang Zhang & Li-Jin Zhu

Authors
  1. Hong-Jing Sun
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  2. Fang-Fang Zhang
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  3. Qing Xiao
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  4. Jia Xu
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  5. Li-Jin Zhu
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Correspondence to Li-Jin Zhu.

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The original online version of this article was revised: Under the header “Introduction”, in the last paragraph, the text ‘showed that MEG3 was downregulated in REP-choroid samples of AMD patients. We also’ was deleted.

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Sun, HJ., Zhang, FF., Xiao, Q. et al. lncRNA MEG3, Acting as a ceRNA, Modulates RPE Differentiation Through the miR-7-5p/Pax6 Axis. Biochem Genet 59, 1617–1630 (2021). https://doi.org/10.1007/s10528-021-10072-9

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