Reactive Oxygen Species Modulator 1 Promotes Tumor Progression and Angiogenesis via the ROS–HIF-1α Axis in Lung Adenocarcinoma

PurposeReactive oxygen species modulator 1 (Romo1) regulates intracellular reactive oxygen species (ROS) production.It has been reported to be upregulated in various cancers and contributes to tumor growth and metastasis.However, the role of Romo1 in tumor angiogenesis remains unclear. Materials and Methods Bioinformatic analysis assessed Romo1 expression and clinical significance in LUAD.Romo1 overexpression and knockdown were used to examine ROS production and expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGFA).YC-1, a HIF-1α inhibitor, was used to determine whether these effects are mediated by Romo1induced HIF-1α upregulation.Pathway enrichment analysis and HIF-1α signature scoring were performed. ResultsRomo1 is highly expressed in LUAD and is associated with aggressive pathological features and a poor prognosis.Romo1 induced ROS production and increased the expression of HIF-1α and VEGFA.Pathway enrichment analysis linked Romo1-associated oxidative stress to the HIF-1 signaling pathway and angiogenesis.Romo1 enhanced the angiogenic activity of endothelial cells and tumor cell proliferation.In a mouse xenograft tumor model, Romo1 promoted tumor growth and angiogenesis through HIF-1α upregulation.HIF-1α inhibition suppressed Romo1-induced tumor cell proliferation and the angiogenic activities.Analysis of the LUAD dataset revealed a positive association between ROMO1 mRNA expression and HIF-1α signaling pathway activation. Conclusion