biostudies-literatureKorde AU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)NHLBI NIH HHSU.S. Department of Defense (United States Department of Defense)511https://www.ebi.ac.uk/biostudies/studies/S-EPMC11953391biostudies-literatureUnknown8(1)Cigarette smoke (CS) creates a "cancer field" in the lung that promotes malignant transformation. The molecular changes within this field are not fully characterized. We examined the significance of microRNA-1 (miR-1) downregulation as one of these changes. We found that tumor miR-1 levels in three non-small cell lung cancer cohorts show inverse correlations with the smoking burden. Lung MiR-1 levels follow a spatial gradient, have prognostic significance, and correlate inversely with the molecular markers of injury. In CS-exposed lungs, miR-1 is specifically downregulated in the endothelium. Exposure to CS induces angiogenesis by selectively degrading mature miR-1 via a vascular endothelial growth factor-driven pathway. Applying a multi-step molecular screen, we identified angiogenic geneCommunications biologyCigarette smoke induces angiogenic activation in the cancer field through dysregulation of an endothelial microRNA.PMC11953391R01 HL155948R01CA225977R00 HL098695PR211314Diao LKorde AZhang JGAnderson SBoffa DJHu BWang JYan XMoghaddam SJVelasco WVPuchalski JTTakyar SSRamaswamy ASauler MPisani MAJin LfalseCigarette smoke induces angiogenic activation in the cancer field through dysregulation of an endothelial microRNA.Cigarette smoke (CS) creates a "cancer field" in the lung that promotes malignant transformation. The molecular changes within this field are not fully characterized. We examined the significance of microRNA-1 (miR-1) downregulation as one of these changes. We found that tumor miR-1 levels in three non-small cell lung cancer cohorts show inverse correlations with the smoking burden. Lung MiR-1 levels follow a spatial gradient, have prognostic significance, and correlate inversely with the molecular markers of injury. In CS-exposed lungs, miR-1 is specifically downregulated in the endothelium. Exposure to CS induces angiogenesis by selectively degrading mature miR-1 via a vascular endothelial growth factor-driven pathway. Applying a multi-step molecular screen, we identified angiogenic gene2025-01-01T00:00:00Z2025 Mar2026-06-02T20:38:20.311Z2025-06-25T03:04:39.015ZS-EPMC119533914015574910.1038/s42003-025-07710-y