AUTHOR=He Yanyan , Duan Lin , Wu Haigang , Chen Song , Lu Taoyuan , Li Tianxiao , He Yingkun 

TITLE=Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.731414

DOI=10.3389/fonc.2021.731414

ISSN=2234-943X

ABSTRACT=<p>Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage of photodynamic intervention (PDT) significantly affects the expression of cellular biomarkers. To understand the impact of photodynamic interventions on cerebrovascular endothelial cells, we evaluated the dosage-dependent impact of porfimer sodium-mediated PDT on B.END3 cells using flow cytometer, comet assay, RNA sequencing, and bioinformatics analysis. To examine whether PDT can induce disorder of intracellular organelles, we did not observe any significance damage of DNA and cellular skeleton. Moreover, expression levels of cellular transporters-related genes were significantly altered, implying the drawbacks of PDT on cerebrovascular functions. To address the potential molecular mechanisms of these phenotypes, RNA sequencing and bioinformatics analysis were employed to identify critical genes and pathways among these processes. The gene ontology (GO) analysis and protein-protein interaction (PPI) identified 15 hub genes, highly associated with cellular mitosis process (<italic>CDK1</italic>, <italic>CDC20</italic>, <italic>MCM5</italic>, <italic>MCM7</italic>, <italic>MCM4</italic>, <italic>CCNA2</italic>, <italic>AURKB</italic>, <italic>KIF2C</italic>, <italic>ESPL1</italic>, <italic>BUB1B</italic>) and DNA replication (<italic>POLE2</italic>, <italic>PLOE</italic>, <italic>CDC45</italic>, <italic>CDC6</italic>). Gene set enrichment analysis (GSEA) reveals that <italic>TNF-α/NF-κB</italic> and <italic>KRAS</italic> pathways may play a critical role in regulating expression levels of transporter-related genes. To further perform qRT-PCR assays, we find that <italic>TNF-α/NF-κB</italic> and <italic>KRAS</italic> pathways were substantially up-regulated, consistent with GSEA analysis. The current findings suggested that a low dosage of PDT intervention may be detrimental to the homeostasis of blood-brain barrier (BBB) by inducing the inflammatory response and affecting the expression of surface biomarkers.</p>