Long non-coding RNA Gas5 potentiates the effects of microRNA-21 downregulation in response to ischaemic brain injury.
Brain ischaemia, which can cause severe nerve injury, is a global health challenge. Long non-coding RNA (lncRNA) growth-arrest specific 5 (Gas5) has been documented to exert tumour suppressive effects in several cancers. However, its role in cerebrovascular disease still requires further investigation. Therefore, in this study, we focused on the role of lncRNA regulatory signalling related to lncRNA Gas5 in ischaemic brain injury. Middle cerebral artery occlusion (MCAO) was employed as a model of ischaemic brain injury in rats. The expression of lncRNA Gas5 and microRNA-21 (miR-21) was altered in neurons to elucidate their effects in ischaemic brain injury and to identify the interactions among lncRNA Gas5, miR-21 and Pten. The neuronal survival rate, apoptosis and the expression of phosphatidyl inositol 3-kinase (PI3K)/Akt signalling pathway-related genes were also evaluated in vitro to determine the effects of lncRNA Gas5. In the brains of rats subjected to MCAO, the expression of lncRNA Gas5 and Pten was upregulated, while miR-21 was downregulated. LncRNA Gas5 inhibited miR-21 expression, leading to elevated levels of Pten. In vitro experiments revealed that lncRNA Gas5 depletion and miR-21 elevation resulted in the suppression of neuronal apoptosis, thus promoting neuronal survival via the PI3K/Akt signalling pathway. These findings demonstrate that lncRNA Gas5 increases miR-21 and activates Pten, contributing to the development of ischaemic brain injury, supporting the silencing of lncRNA Gas5 as a possible therapeutic target for the treatment of ischaemic brain injury.
['Li|Jie|J|', 'Lv|Hui|H|', 'Che|Yu-Qin|YQ|']
D000818:Animals D001930:Brain Injuries D015536:Down-Regulation D035683:MicroRNAs D019869:Phosphatidylinositol 3-Kinases D062085:RNA, Long Noncoding D051381:Rats
microRNA-21 ischaemic brain injury neuronal apoptosis PI3K/Akt signalling pathway long non-coding RNA growth-arrest specific 5 phosphatase and tensin homologue