Long non-coding RNA H19 protects against intracerebral hemorrhage injuries via regulating microRNA-106b-5p/acyl-CoA synthetase long chain family member 4 axis.

Abstract

Intracerebral hemorrhage (ICH) is one of the most common refractory diseases. Long non-coding RNAs (lncRNAs) play crucial roles in ICH. This study was designed to investigate the role of lncRNA H19 in ICH and the underlying molecular mechanisms involved. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine mRNA expression. Cell viability was analyzed using Cell Counting Kit 8 (CCK8). PI staining Flow cytometry and TdT-mediated biotinylated nick end-labeling (TUNEL) assays were performed to determine ferroptosis in brain microvascular endothelial cells (BMVECs). Targeting relationships were predicted using Starbase and TargetScan and verified by RNA pull-down and luciferase reporter gene assays. Western blotting was performed to assess protein expression. LncRNA H19 is highly expressed in ICH model cells. Over-expression of H19 suppressed cell viability and promoted ferroptosis of BMVECs. miR-106b-5p is predicted to be a target of H19. The expression of miR-106b-5p was lower in oxygen and glucose deprivation hemin-treated (OGD/H-treated) cells. Over-expression of miR-106b-5p reversed the effects of H19 on cell viability and ferroptosis in BMVECs. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) was verified to be a target gene of miR-106b-5p and was highly expressed in OGD/H-treated cells. Upregulation of ACSL4 inhibited the effects of miR-106b-5p and induced BMVEC dysfunction. In conclusion, lncRNA H19 was overexpressed in ICH. Knockdown of H19 promoted cell proliferation and suppressed BMVECs ferroptosis by regulating the miR-106b-5p/ACSL4 axis. Therefore, H19 knockdown may be a promising therapeutic strategy for ICH.

• Authors: Bing Chen, Haoran Wang, Chenglin Lv, Chongdan Mao, Yuguang Cui
• Journal: Bioengineered (Bioengineered) Vol. 12 Issue 1 Pg. 4004-4015 (12 2021) ISSN: 2165-5987 [Electronic] United States
• PMID: 34288826 (Publication Type: Journal Article)

Chemical References

• H19 long non-coding RNA
• MIRN106 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Coenzyme A Ligases
• long-chain-fatty-acid-CoA ligase
• Glucose
• Oxygen

Topics

• Base Sequence
• Brain (blood supply)
• Cell Survival (genetics)
• Cerebral Hemorrhage (genetics, prevention & control)
• Coenzyme A Ligases (genetics)
• Down-Regulation (genetics)
• Endothelial Cells (metabolism)
• Ferroptosis (genetics)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Glucose (deficiency)
• Humans
• MicroRNAs (genetics, metabolism)
• Microvessels (pathology)
• Models, Biological
• Oxygen
• RNA, Long Noncoding (genetics, metabolism)
• Up-Regulation (genetics)