Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression

Abstract

ObjectiveOur previous work found COX4I2 was associated with angiogenesis in pheochromocytoma. The purpose of this study was to explore the role of COX4I2 in regulating angiogenesis in pheochromocytoma.MethodsDistribution of COX4I2 was evaluated by scRNA-seq in one case of pheochromocytoma and the findings were verified by immunostaining. COX4I2 was further knocked down in target cells. Changes of angiogenesis-related genes were evaluated by qPCR in target cells.ResultsThe scRNA-seq revealed high mRNA expression of COX4I2 in fibroblasts rather than tumor cells. Immunostaining of COX4I2 confirmed its distribution in fibroblasts. Knocking down COX4I2 in NIH3T3 cell line led to significant reduction of angiogenesis-related genes, especially ANG1 and HGF.ConclusionsFibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression, possibly by affecting ANG1 and HGF.

Runx1 is upregulated by STAT3 and promotes proliferation of neonatal rat cardiomyocytes

“…Interestingly, cardiac fetal genes such as Acta1 (Chien et al., 1991 ), Cnn1 (Samaha et al., 1996 ), Nppa (Chien et al., 1991 ), Nppb (Barry et al., 2008 ), Myl4 (Hernandez et al., 2007 ), Hand1 (Okubo et al., 2021 ), Atp1a3 (Charlemagne et al., 1994 ), Pfkp (Shen et al., 2020 ), Pgm1 (Guo & Pu, 2020 ; Liu et al., 2023 ; Sim et al., 2015 ), Ccnd1 (Ikenishi et al., 2012 ), and Ccnd2 (Guo & Pu, 2020 ) were increased in Runx1‐overexpressing NRCMs (Figure 5b ; Table S4 ). Conversely, genes associated with fatty acid oxidation or electron transport chain such as Acsl1 (Goldenberg et al., 2016 ), Cpt1a (Schlaepfer & Joshi, 2020 ), Acad11 (Swigonová et al., 2009 ), Ech1 (Huang et al., 2018 ), Cox4i2 (Mao et al., 2022 ), and Cox8b (DeLaughter et al., 2016 ) were decreased by Runx1 overexpression (Figure 5c ; Table S5 ). Considering that fatty acid oxidation and electron transport chain are activated in mature cardiomyocytes, these data propose that the expression of Runx1 induced the juvenilization of NRCMs.…”