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LncRNA THRIL promotes high glucose-induced proliferation and migration of human retina microvascular endothelial cells through enhancing autophagy

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Abstract

Aims

Diabetes retinopathy (DR) is associated with retinal microvascular system injury induced by high glucose (HG). This study aims to explore the role and mechanism of long non-coding RNA THRIL in regulating cell proliferation and migration of human retina microvascular endothelial cells (hRMECs) under HG condition.

Method

The gene and protein expression were detetced by RT-PCR and western blot, respectively. Cell proliferation and migration of hRMECs were examined using MTT assay and Transwell assay, respectively. The interaction between miR-125b-5p and THRIL or autophagy-related gene 4D (ATG4D) was analyzed using luciferase activity assay.

Results

THRIL expression was induced by HG in hRMECs. THRIL overexpression enhanced the proliferation and migration of hRMECs induced by HG, whereas THRIL silencing yielded the opposite results. Furthermore, THRIL overexpression induced autophagy activation, and inhibition of autophagy by 3-methyladenine abrogated the promotory effects of THRIL overexpression on cell proliferation and migration of hRMECs. Mechanismly, THRIL inhibited miR-125b-5p to upregulate the expression of ATG4D (an important autophagy-related gene), thereby promoting autophagy. Moreover, miR-125b-5p overexpression or ATG4D silencing alone abolished the promoting effects of THRIL overexpression on HG-induced autophagy, proliferation and migration of hRMECs.

Conclusions

THRIL promotes HG-induced cell proliferation and migration of hRMECs through activation of autophagy via the miR-125b-5p/ATG4D axis. THRIL may serve as a potential therapeutic target for DR.

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Availability of data and materials

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

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Acknowledgements

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Funding

This study was supported by grants from Natural Science Foundation of Anhui (1908085MH253).

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Authors and Affiliations

  1. Department of Ophthalmology, Affiliated First Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, 230001, China

    Qingshan Ji, Jing Han, Jiajia Liu, Huayi Lv, Lisong Wang, Yiran Dong & Lei Shi

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  1. Qingshan Ji
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  4. Huayi Lv
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  5. Lisong Wang
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  7. Lei Shi
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Contributions

QJ, JH designed the study; all authors participated in the experiments; QJ, JH, LS contributed the data analysis; QJ drafted the paper; JH revised the paper. All authors approved the paper.

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Correspondence to Lei Shi.

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The authors declare no conflicts of interest.

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This study was approved by the Ethics Committee of The First Affiliated Hospital of USTC.

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No human samples were involved in this study.

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Qingshan Ji and Jing Han are co-first authors.

This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques.

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Ji, Q., Han, J., Liu, J. et al. LncRNA THRIL promotes high glucose-induced proliferation and migration of human retina microvascular endothelial cells through enhancing autophagy. Acta Diabetol 59, 369–380 (2022). https://doi.org/10.1007/s00592-021-01813-8

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