PLAT and central nervous system cancer: Gu et al. (2016) observed upregulation of HMGB1 upon down-regulation of miR-218 in gliomas, a feature that we also detected in our lung cells by immunoblotting. Upregulated HMGB1 will contribute to the disruption of endothelial barrier function as HMGB1 has been shown to down regulate adherence and tight junction proteins VE-cadherin and ZO-1 in lung endothelial cells (Luan et al., 2018). HMGB1 has also been shown in human microvascular endothelial cells to directly increase expression of ICAM1, VCAM1, TNFα, IL8, PAI1, and tPA (Fiuza et al., 2003).