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

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.

• Authors: Xiamin Hu, Fuyun Ma, Zhongliang Cheng, Suyou Zeng, Ruling Shen, Xuan Li, Junqi Hu, Zhigang Jin, Jinping Cheng
• Journal: Aging (Aging (Albany NY)) Vol. 14 Issue 12 Pg. 5177-5194 (06 24 2022) ISSN: 1945-4589 [Electronic] United States
• PMID: 35749138 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN874 microRNA, mouse
• MicroRNAs
• RNA, Long Noncoding
• Glucose

Topics

• Animals
• Apoptosis (physiology)
• Autophagy (physiology)
• Brain Ischemia (genetics, metabolism, pathology)
• Glucose (metabolism)
• Infarction, Middle Cerebral Artery (genetics, metabolism, pathology)
• Ischemic Stroke (genetics, metabolism, pathology)
• Male
• Mice
• MicroRNAs (genetics, metabolism)
• RNA, Long Noncoding (genetics)
• Reperfusion Injury (genetics, metabolism, pathology)
• Stroke (genetics, metabolism, pathology)