RNA Sequencing Gene Expression Profiles in Wild-Type and MLK2 and MLK3 double knockout (MLK2-/-MLK3-/-) Mouse Lung Endothelial Cells Under Normoxic and Hypoxic Conditions
MLK2 and MLK3 are key regulators of angiogenesis, particularly under hypoxic conditions. To investigate the underlying mechanisms, we performed unbiased RNA sequencing on primary lung endothelial cells isolated from wild-type and MLK2 and MLK3 double knockout (MLK2-/-MLK3-/-) mice exposed to normoxia or hypoxia. Transcriptomic analysis revealed significant enrichment of the “Pathways in cancer” and “HIF1a signaling pathway,” which regulate proangiogenic genes. Our RNA Seq data suggest that, mechanistically, MLKs act through the long noncoding RNA H19 to regulate angiogenic gene expression. These findings identify the MLK-H19 axis as a critical regulator of endothelial function and a key driver of tumor-associated angiogenesis Overall design: In order to identify downstream pathways of MLK family, RNA was extracted from C57BL/6J and MLK2-/-MLK3-/- MLECs grown under hypoxia (1% oxygen for 90 minutes) or normoxia (21% oxygen) and RNA seq analysis was performed.