MicroRNA-760 Resists Ambient PM2.5-induced Lung Injury Through Upregulating Heme-oxygenase 1 Expression (preprint)

ABSTRACT

Background: PM2.5 (particles matter smaller aerodynamic diameter of 2.5 μm ) exposure, as one major environmental risk factor for the global burden of disease, is associated with high risks of respiratory diseases and lung cancer. Heme-oxygenase 1 (HMOX1) has been considered as one of the major molecular antioxidant defenses to mediate cytoprotective effects against diverse stressors, including PM2.5-induced toxicity and SARS-CoV-2 infection; however, the regulatory mechanism of HMOX1 expression still needs to be elucidated. In this study, using PM2.5 as a typical stressor, we explored whether microRNAs (miRNAs) might modulate HMOX1 expression in lung cells. Results: Systematic bioinformatics analysis showed that seven miRNAs have the potential to target HMOX1 gene. Among these, hsa-miR-760 was identified as a response miRNA to PM2.5 exposure. More importantly, we revealed a “non-conventional” miRNA function in hsa-miR-760 upregulating HMOX1 expression, by targeting the coding region and interacting with YBX1 protein. In addition, we observed that exogenous hsa-miR-760 effectively elevated HMOX1 expression, reduced the reactive oxygen agents (ROS) levels, and then rescued the lung cells from PM2.5-induced apoptosis. Conclusion: Our results revealed that hsa-miR-760 might play an important role in protecting lung cells against PM2.5-induced toxicity, by elevating HMOX1 expression, and offered new clues to elucidate the diverse function of miRNAs.