Open Access

ARTICLE

CircR-ZC3HC1 mediates MiR-384-5p/SIRT1 axis to promote neuronal autophagy and relieves ischemic stroke

MIN SHEN^1,2, XIAOMAN XU^1,2, GUANGLING SUN¹, LIANGZHU WANG¹, TAO YING¹, HANG SU¹, WEI WANG¹, QINGHUA CAO^1,*, ZHEZHE SUN^1,*

1 Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, China
2 School of Medicine, Ningbo University, Ningbo, 315211, China

* Corresponding Authors: QINGHUA CAO. Email: ; ZHEZHE SUN. Email:

BIOCELL 2024, 48(3), 491-499. https://doi.org/10.32604/biocell.2023.047640

Received 13 November 2023; Accepted 11 December 2023; Issue published 15 March 2024

Abstract

Objective: Circular RNAs (circRNAs) have been shown to involve in pathological processes of ischemic stroke (IS), including autophagy. This study was designed to explore the effect of circR-ZC3HC1 on neuronal autophagy in IS and the related mechanisms. Methods: Expression of circR-ZC3HC1 in blood samples of IS patients and healthy controls was detected. Hippocampal neurons were treated with oxygen and glucose deprivation (OGD) to establish IS in vitro model. The expression of LC3 and p62 and the number of autophagosomes were examined to evaluate the autophagy level of OGD induced neurons using western blotting and transmission electron microscope. Cell apoptosis rate and the expression of cleaved caspase-3, Bax, and Bcl-2 were assessed by flow cytometry and western blotting. The binding relationships among circR-ZC3HC1, miR-384-5p, and SIRT1 were predicted and verified. Results: Low expression of circR-ZC3HC1 was found in blood samples of IS patients and OGD-treated neurons. Overexpressed circR-ZC3HC1 or inhibited miR-384-5p expression promoted autophagy and inhibited apoptosis of OGD-treated neurons, which could be reversed by further 3-MA treatment. Mechanistically, circR-ZC3HC1 targeted miR-384-5p to mediate SIRT1 expression. miR-384-5p overexpression or SIRT1 knockdown in the presence of circR-ZC3HC1 overexpression in OGD-treated neurons lead to reduced autophagy and enhanced apoptosis. Conclusion: Collectively, circR-ZC3HC1 promoted neuronal autophagy to attenuate IS via miR-384-5p/SIRT1 axis.

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Keywords

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