KCNQ1OT1 Exacerbates Ischemia-Reperfusion Injury Through Targeted Inhibition of miR-140-3P.

Abstract

Potassium voltage-gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1), a long non-coding RNA found in the KCNQ1 locus, has been evidenced to play important roles in the aggravation of inflammatory and oxidative stresses under hypoxia, but whether and how KCNQ1OT1 contributes to neuronal damages in the cerebral ischemic stroke remains unknown. In the present study, we found a dominant upregulation of KCNQ1OT1 both in the plasma of cerebral ischemia patients and in an oxygen-glucose deprivation and reperfusion (OGD/R) model in PC12 cells. KCNQ1OT1 knocking-down significantly ameliorated the inflammation, oxidative stress, and cell apoptosis induced by OGD/R. We further demonstrated that KCNQ1OT1 directly bound to and suppressed the expression of miR-140-3p. Overexpressing miR-140-3p significantly alleviated both the inflammation, oxidative stress, and cell apoptosis in OGD/R, while all those cytoprotective effects of miR-140-3p-overexpression were hindered by the co-overexpression of KCNQ1OT1. Furthermore, we found a direct interaction between miR-140-3p and the hypoxia-inducible factor-1α (HIF-1α), which was suppressed by the upregulation of KCNQ1OT1 in OGD/R. Our results indicate that KCNQ1OT1 exacerbates cerebral ischemia-reperfusion injury by targeted binding to miR-140-3p, thus interfering its direct interaction with HIF-1α. These data provide novel therapeutic targets in the cerebral ischemic stroke.

• Authors: Ming Yi, Yue Li, Dan Wang, Qiuxia Zhang, Li Yang, Chunsheng Yang
• Journal: Inflammation (Inflammation) Vol. 43 Issue 5 Pg. 1832-1845 (Oct 2020) ISSN: 1573-2576 [Electronic] United States
• PMID: 32519270 (Publication Type: Journal Article)

Chemical References

• KCNQ1OT1 long non-coding RNA, human
• MicroRNAs
• Mirn140 microRNA, human
• Potassium Channels, Voltage-Gated
• RNA, Small Interfering

Topics

• Animals
• Brain Ischemia (metabolism, pathology)
• Gene Knockdown Techniques (methods)
• Humans
• MicroRNAs (antagonists & inhibitors, metabolism)
• PC12 Cells
• Potassium Channels, Voltage-Gated (deficiency, metabolism)
• Protein Binding
• RNA, Small Interfering (pharmacology)
• Rats
• Reperfusion Injury (metabolism, pathology)