The Neuroprotection Effect and Mechanism of Long Non-Coding RNA MALAT1 in Acute Ischemic Stroke

Stroke is the 3rd leading cause of death in Taiwan and the survivors of stroke usually have handicap. At present most neuroprotective strategies failed to improve patients’ neurological outcome in clinical trials. There have been many studies showing the substantial role of gene in the stroke outcome. Noncoding RNA (ncRNA) has been found to modulate many mRNA and protein in many diseases: A major category of ncRNA is "long noncoding RNA (lncRNA)".The studies of their roles and mechanisms in the stroke outcome are still lacking. Our team has found the expression of cancer related lncRNA "MALAT1" would increase in the ischemia of human neuroblastoma cell line SH-SY5Y. In the past studies, MALAT1 has been found increased in the ischemia of endothelial cell lines and in the peripheral blood of patients with acute myocardial infarction. Therefore, we hypothesized that the MALAT1 would have important association with the mechanisms in the vascular diseases such as inflammation, apoptosis, and angiogenesis. We have found the MALAT1 knockdown of SH-SY5Y would increase the survival in the ischemia compared to non-MALAT1 knockdown control. Therefore, MALAT1 is a potential therapeutic target in ischemic stroke. This proposal is a one-year-project: to prove the therapeutic effect and mechanisms of MALAT1 in ischemic stroke by using the ischemic animal model with MALAT1 knockdown techniques.