John Libbey Eurotext

lncRNA UCA1 induces autophagic gene expression via epigenetic regulation mediated by ATG16L1 and miR-132-3p in SH-SY5Y cells treated with retinoic acid Article à paraître

Illustrations

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Tableaux

Auteurs
1 Department of Neurology, The Second Xiang Ya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China
2 Department of Neurosurgery, The Second Xiang Ya Hospital of Central South University, Changsha 410011, Hunan Province, P.R. China
Correspondence:
Jun Xiang
Department of Neurosurgery, The Second Xiang Ya Hospital of Central South University, No. 139 Renmin Road, Changsha 410011, Hunan Province, P.R. China

Objective

Epilepsy is a chronic brain disease with recurrent seizures. Autophagy plays a crucial role in the progression of epilepsy. This study aimed to explore the function and intrinsic mechanism of the long non-coding RNA (lncRNA) UCA1/miR-132-3p/ATG16L1 axis in epilepsy via regulation of autophagy.

Methods

The expression of lncRNA UCA1, miR-132-3p and ATG16L1 was measured in serum from epileptic patients by quantitative RT-PCR. A SH-SY5Y cell model was further constructed using retinoic acid to investigate the UCA1/ miR-132-3p/ATG16L1 axis by quantitative RT-PCR, western blotting, fluorescence in situ hybridisation, RNA immunoprecipitation, chromatin immunoprecipitation, and a dual-luciferase reporter gene assay.

Results

In the serum of epileptic patients, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated, compared to controls. Similarly, in the SH-SY5Y cell model, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated in retinoic acid-treated cells; lncRNA UCA1 was mainly located in the cytoplasm. lncRNA UCA1 overexpression was shown to promote autophagic gene expression, which was reversed by miR-132-3p overexpression. Moreover, autophagic gene expression induced by miR-132-3p knockdown was reversed by ATG16L1 knockdown. Based on precipitation assays, lncRNA UCA1 and miR-132-3p were shown to form a complex with the transcription factor, EZH2, and miR-132-3p was shown to interact with ATG16L1 based on a luciferase assay. Finally, lncRNA UCA1 was shown to negatively regulate miR-132-3p expression, and miR-132-3p was shown to negatively regulate ATG16L1.

Significance

In this cell model, lncRNA UCA1 promotes autophagic gene expression via epigenetic regulation mediated by ATG16L1 and miR-132-3p.