AUTHOR=Wan Ding , Feng Jin , Wang Peng , Yang Zhenxing , Sun Tao 

TITLE=Hypoxia- and Inflammation-Related Transcription Factor SP3 May Be Involved in Platelet Activation and Inflammation in Intracranial Hemorrhage

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.886329

DOI=10.3389/fneur.2022.886329

ISSN=1664-2295

ABSTRACT=The purpose of this study was to identify the biomarkers implicated in the development of intracranial hemorrhage (ICH), as well as potential regulatory pathways. In transcriptomic data for patients with ICH, we identified DEmiRNAs and DEmRNAs related to hypoxia, inflammation, and their transcription factors (TFs). A ICH-based miRNA-TF-mRNA regulatory network was thus constructed, and four biomarkers (TIMP1, PLAUR, DDIT3 and CD40) were screened for their association with inflammation or hypoxia by machine learning. Following this, SP3 was found to be a transcription factor involved in hypoxia and inflammation, which regulates TIMP1 and PLAUR. From the constructed miRNA-TF-mRNA regulatory network, we identified three axes, hsa-miR-940/RUNX1/TIMP1, hsa-miR-571/SP3/TIMP1 and hsa-miR-571/SP3/PLAUR, which may be involved in the development of ICH. Upregulated TIMP1 and PLAUR were validated in an independent clinical cohort three days after ICH onset. According to Gene Set Enrichment Analysis (GSEA), SP3 was discovered to be important in interleukin signaling and platelet activation for hemostasis. Transcription factor SP3 associated with hypoxia or inflammation play important roles in ICH development. This study provides potential targets for monitoring the severity of inflammation and hypoxia in patients with ICH.