PMID- 34091825 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20220207 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 58 IP - 9 DP - 2021 Sep TI - Circulating lncRNAs HIF1A-AS2 and LINLK-A: Role and Relation to Hypoxia-Inducible Factor-1alpha in Cerebral Stroke Patients. PG - 4564-4574 LID - 10.1007/s12035-021-02440-8 [doi] AB - Long noncoding RNAs (lncRNAs) have been recently recognized as key players of gene expression in cerebral pathogenesis. Thus, their potential use in stroke diagnosis, prognosis, and therapy is actively pursued. Due to the complexity of the disease, identifying stroke-specific lncRNAs remains a challenge. This study investigated the expression of lncRNAs HIF1A-AS2 and LINK-A, and their target gene hypoxia-inducible factor-1 (HIF-1) in Egyptian stroke patients. It also aimed to determine the molecular mechanism implicated in the disease. A total of 75 stroke patients were divided into three clinical subgroups, besides 25 healthy controls of age-matched and sex-matched. Remarkable upregulation of lncRNA HIF1A-AS2 and HIF1-alpha along with a downregulation of lncRNA LINK-A was noticed in all stroke groups relative to controls. Serum levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt (p-Akt), vascular endothelial growth factor (VEGF), and angiopoietin-1 (ANG1) as well as their receptors, malondialdehyde (MDA), and total antioxidant capacity (TAC) were significantly increased, whereas brain-derived neurotrophic factor (BDNF) levels were significantly decreased particularly in hemorrhagic stroke versus ischemic groups. Eventually, these findings support the role of lncRNAs HIF1A-AS2 and LINK-A as well as HIF1-alpha in activation of angiogenesis, neovascularization, and better prognosis of stroke, especially the hemorrhagic type. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Ewida, Heba A AU - Ewida HA AD - Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), Cairo, Egypt. FAU - Zayed, Rana K AU - Zayed RK AD - Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), Cairo, Egypt. FAU - Darwish, Hebatallah A AU - Darwish HA AUID- ORCID: 0000-0001-5482-5559 AD - Pharmacology, Toxicology and Biochemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), Cairo, Egypt. Hebatallah.darwish@pharma.cu.edu.eg. AD - Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Hebatallah.darwish@pharma.cu.edu.eg. FAU - Shaheen, Amira A AU - Shaheen AA AD - Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. LA - eng PT - Journal Article DEP - 20210605 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Angiopoietin-1) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (RNA, Long Noncoding) RN - 0 (Vascular Endothelial Growth Factor A) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Adult MH - Aged MH - Angiopoietin-1/blood MH - Down-Regulation MH - Female MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*blood MH - Male MH - Malondialdehyde/blood MH - Middle Aged MH - Oxidative Stress/*physiology MH - Phosphatidylinositol 3-Kinases/blood MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/blood MH - RNA, Long Noncoding MH - Stroke/*blood MH - Up-Regulation MH - Vascular Endothelial Growth Factor A/blood OTO - NOTNLM OT - Cerebral stroke OT - HIF1-alpha OT - Non-invasive stroke biomarkers OT - lncRNA HIF1A-AS2 OT - lncRNA LINK-A EDAT- 2021/06/07 06:00 MHDA- 2022/02/08 06:00 CRDT- 2021/06/06 21:17 PHST- 2021/03/18 00:00 [received] PHST- 2021/05/25 00:00 [accepted] PHST- 2021/06/07 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/06/06 21:17 [entrez] AID - 10.1007/s12035-021-02440-8 [pii] AID - 10.1007/s12035-021-02440-8 [doi] PST - ppublish SO - Mol Neurobiol. 2021 Sep;58(9):4564-4574. doi: 10.1007/s12035-021-02440-8. Epub 2021 Jun 5.