Hsa_circ_0017109 Facilitates Formaldehyde-induced Pulmonary Epithelial Mesenchymal Transition via the miR-191-5p/CDK6...

Formaldehyde (FA) is a ubiquitous environmental pollutant and a classified Group I carcinogen that poses significant respiratory health risks. Although circular RNAs (circRNAs) are known regulators in various pathologies, their specific roles in FA-induced lung injury remain poorly understood. This study aims to elucidate the function and underlying mechanism of hsa_circ_0017109 in FA-induced pulmonary epithelial-mesenchymal transition (EMT). We established FA exposure models using BEAS-2B cells and Balb/c mice. In vitro, both short- and long-term FA exposure induced a mesenchymal-like morphology, promoted cell proliferation and migration, and upregulated EMT markers (N-cadherin, ZEB1) while downregulating E-cadherin. Consistent with these findings, in vivo FA inhalation caused dose-dependent lung histological damage, ranging from alveolar thickening to collapse, and triggered EMT-like changes in lung tissues. Mechanistically, hsa_circ_0017109 was significantly upregulated in FA-exposed cells. Functional assays demonstrated that hsa_circ_0017109 knockdown attenuated FA-induced EMT. Further investigation revealed that hsa_circ_0017109 acts as a competing endogenous RNA (ceRNA) for miR-191-5p, thereby relieving the repression of its downstream target, Cyclin Dependent Kinase 6 (CDK6). Consequently, the accumulated CDK6 facilitates the EMT process. In conclusion, our findings characterize a novel hsa_circ_0017109/miR-191-5p/CDK6 regulatory axis that drives FA-induced pulmonary EMT, highlighting hsa_circ_0017109 as a potential biomarker and therapeutic target for FA-associated lung injury.