(Peer-Reviewed) Essential role of MALAT1 in reducing traumatic brain injury
Na Wu ¹, Chong-Jie Cheng 程崇杰 ¹, Jian-Jun Zhong 钟建军 ¹, Jun-Chi He 何骏驰 ¹, Zhao-Si Zhang 张兆斯 ¹, Zhi-Gang Wang ¹, Xiao-Chuan Sun 孙晓川 ¹, Han Liu 刘汉 ¹ ²
¹ Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
中国 重庆 重庆医科大学附属第一医院神经外科
² Department of Neurosurgery, Qilu Hospital of Shandong University (Qingdao Campus), Qingdao, Shandong Province, China
中国 山东 青岛 山东大学齐鲁医院（青岛）神经外科
As a highly evolutionary conserved long non-coding RNA, metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was first demonstrated to be related to lung tumor metastasis by promoting angiogenesis. To investigate the role of MALAT1 in traumatic brain injury, we established mouse models of controlled cortical impact and cell models of oxygen-glucose deprivation to mimic traumatic brain injury in vitro and in vivo.
The results revealed that MALAT1 silencing in vitro inhibited endothelial cell viability and tube formation but increased migration. In MALAT1-deficient mice, endothelial cell proliferation in the injured cortex, functional vessel density and cerebral blood flow were reduced. Bioinformatic analyses and RNA pull-down assays validated enhancer of zeste homolog 2 (EZH2) as a downstream factor of MALAT1 in endothelial cells.
Jagged-1, the Notch homolog 1 (NOTCH1) agonist, reversed the MALAT1 deficiency-mediated impairment of angiogenesis. Taken together, our results suggest that MALAT1 controls the key processes of angiogenesis following traumatic brain injury in an EZH2/NOTCH1-dependent manner.