Research Paper|Volume 14, Issue 12|pp 5177—5194

LncRNA PEG11as silencing sponges miR-874-3p to alleviate cerebral ischemia stroke via regulating autophagy in vivo and in vitro

Xiamin Hu¹, Fuyun Ma¹, Zhongliang Cheng², Suyou Zeng², Ruling Shen³, Xuan Li², Junqi Hu⁴, Zhigang Jin², Jinping Cheng²

¹College of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China
²Wuhan University of Science and Technology Affiliated Wuhan Resources and Wisco General Hospital, Wuhan, Hubei, China
³Shanghai Laboratory Animal Research Center, Shanghai, China
⁴University of California, San Diego, CA 92093, USA

Received: December 28, 2021Accepted: June 14, 2022Published: June 24, 2022

https://doi.org/10.18632/aging.204140

Copyright: © 2022 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long non-coding RNAs (lncRNAs) are reportedly involved in the regulation of physiological and pathophysiological processes. However, the potential role of lncRNAs in stroke remains largely undefined. Here, RNA-Seq analysis of lncRNAs found that the lncRNA PEG11as (PEG11as) levels were significantly increased in ischemic brain tissue in a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) mouse model of stroke. To explore the role of PEG11as in stroke, the lentivirus containing PEG11as silencing construct(siRNA-PEG11as) was microinjected intracerebroventricularly into male or transfected to N2a cells and then exposed to tMCAO/R or oxygen-glucose deprivation/reoxygenation (OGD/R). Knockdown of PEG11as expression significantly reduced infarct volume, alleviated neuronal deficits and inhibited neuronal apoptosis in tMCAO/R mice. Mechanistically, as an endogenous microRNA-874-3p (miR-874-3p) sponge, PEG11as silencing inhibited miR-874-3p activity, resulting in downregulation of ATG16L1 expression and subsequent inhibition of neuronal apoptosis by regulating autophagy. Overall, the results of this current study indicate that PEG11as is involved in the pathophysiology of cerebral ischemia, thus providing translational evidence that PEG11as can be envisioned as a novel biomarker or/and therapeutic target for stroke.