MicroRNA-760 resists ambient PM2.5-induced apoptosis in human bronchial epithelial cells through elevating heme-oxygenase 1 expression
2021
Xu, Lin | Zhao, Qianwen | Li, Daochuan | Luo, Jiao | Ma, Wanli | Jin, Yuan | Li, Chuanhai | Chen, Jing | Zhao, Kunming | Zheng, Yuxin | Yu, Dianke
PM₂.₅ (particles matter smaller aerodynamic diameter of 2.5 μm) exposure, a major environmental risk factor for the global burden of diseases, is associated with high risks of respiratory diseases. Heme-oxygenase 1 (HMOX1) is one of the major molecular antioxidant defenses to mediate cytoprotective effects against diverse stressors, including PM₂.₅-induced toxicity; 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. Systematic bioinformatics analysis showed that seven miRNAs have the potentials to target HMOX1 gene. Among these, hsa-miR-760 was identified as the most responsive 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 rescued the lung cells from PM₂.₅-induced apoptosis. 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 functions of miRNAs.
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