Matthew Tai Hei Chan1, Jennie Yuet Yi Wong1, Anthony Ka Tsun Leung1, Gang Lu2, Wai Sang Poon1, Alexander Yuk-Lun Lau3, Wai Yee Chan4, George Kwok Chu Wong5. 1. Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, 4/F, Department of Surgery, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, China. 2. Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, 4/F, Department of Surgery, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, 7/F, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China. 3. Division of Neurology, Department of Medicine and Therapeutics, Chinese University of Hong Kong, 9/F Department, Department of Medicine and Therapeutics, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, China. 4. CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, 7/F, Lo Kwee-Seong Integrated Biomedical Sciences Building, Area 39, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address: chanwy@cuhk.edu.hk. 5. Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, 4/F, Department of Surgery, Lui Che Woo Clinical Sciences Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, NT, Hong Kong, China. Electronic address: georgewong@surgery.cuhk.edu.hk.
Abstract
BACKGROUND: Subarachnoid hemorrhage (SAH) is fatal and detrimental to quality of life. Clinically, options for monitoring are often limited, potentially missing subtle neurological changes especially in low-grade patients. This article reviewed miRNA dysregulation in SAH and analyzed their functional and clinical relevance. METHODS: With adherence to PRISMA guideline, PubMed, EMBASE, GEO and ArrayExpress were searched comprehensively for relevant clinical and animal models. Datasets were analyzed and enriched by experimentally validated targets and multiple databases using R v3.4.2, Ingenuity Pathway Analysis, and miRPath v3.0. RESULTS: Among 1926 search results, 18 studies were screened for full-text assessment. The 8 included studies revealed a marked miRNA dysregulation after SAH. 2 datasets were retrieved. In both serum and CSF, different miRNA profiles were associated with Early Brain Injury, Delayed Cerebral Infarction, vasospasm and prognosis. In CSF, a dramatic restructure of inter-miRNA correlation matrix was observed. Enrichment analysis revealed strong association (1) BBB instability, with adherens, extra-cellular matrix, actin cytoskeleton, integrin, TGF-β, Wnt/β-catenin etc; (2) autophagy, with MTORC1, HIF-1, ULK2, and FoxO etc; (3) apoptosis, with PI3K-Akt, p53, and AMPK. We analyzed common miRNAs across SAH and cerebral ischemia. They were related to neuronal differentiation, oxidation stress, apoptosis, angiogenesis, Alzheimer's disease, NMDA-induced calcium influx, excitotoxicity and NO production. CONCLUSIONS: Clinical progression of SAH is associated with different miRNA fingerprints. They carry neuro-pathological relevance and can be a potential biomarker which compliments SAH management.
BACKGROUND:Subarachnoid hemorrhage (SAH) is fatal and detrimental to quality of life. Clinically, options for monitoring are often limited, potentially missing subtle neurological changes especially in low-grade patients. This article reviewed miRNA dysregulation in SAH and analyzed their functional and clinical relevance. METHODS: With adherence to PRISMA guideline, PubMed, EMBASE, GEO and ArrayExpress were searched comprehensively for relevant clinical and animal models. Datasets were analyzed and enriched by experimentally validated targets and multiple databases using R v3.4.2, Ingenuity Pathway Analysis, and miRPath v3.0. RESULTS: Among 1926 search results, 18 studies were screened for full-text assessment. The 8 included studies revealed a marked miRNA dysregulation after SAH. 2 datasets were retrieved. In both serum and CSF, different miRNA profiles were associated with Early Brain Injury, Delayed Cerebral Infarction, vasospasm and prognosis. In CSF, a dramatic restructure of inter-miRNA correlation matrix was observed. Enrichment analysis revealed strong association (1) BBB instability, with adherens, extra-cellular matrix, actin cytoskeleton, integrin, TGF-β, Wnt/β-catenin etc; (2) autophagy, with MTORC1, HIF-1, ULK2, and FoxO etc; (3) apoptosis, with PI3K-Akt, p53, and AMPK. We analyzed common miRNAs across SAH and cerebral ischemia. They were related to neuronal differentiation, oxidation stress, apoptosis, angiogenesis, Alzheimer's disease, NMDA-induced calcium influx, excitotoxicity and NO production. CONCLUSIONS: Clinical progression of SAH is associated with different miRNA fingerprints. They carry neuro-pathological relevance and can be a potential biomarker which compliments SAH management.
Authors: Zsolt Fejes; Judit Erdei; Marianna Pócsi; Jun Takai; Viktória Jeney; Andrea Nagy; Alíz Varga; Attila Bácsi; László Bognár; László Novák; János Kappelmayer; Béla Nagy Journal: Int J Mol Sci Date: 2020-09-19 Impact factor: 5.923