PM2.5 exposure-induced autophagy is mediated by lncRNA loc146880 which also promotes the migration and invasion of lung cancer cells.

ABSTRACT

BACKGROUND: Evidence shows that individuals who are under long-term exposure to environmental PM2.5 are at increased risk of lung cancer. Various laboratory experiments also suggest several mechanistic links between PM2.5 exposure and lung carcinogenesis. However, a long non-coding RNA (lncRNA) mediated pathogenic change after PM2.5 exposure and its potential roles in tumorigenesis and disease progression have not been reported. METHODS: Cytotoxicity induced by PM2.5 was assessed by using scanning electron microscopy and transmission electron microscopy. ROS generation, autophagy, and metastasis induced by PM2.5 were detected by using comprehensive approaches. Expression of lncRNA-loc146880 and lc3b (autophagy marker) in A549 cells, lung tissue and serum were determined by RT-PCR and Western blotting. RESULTS: PM2.5 could be internalized into lung cancer cells, resulting in marked increases in ROS levels and autophagy. ROS may be responsible for increased expression of loc146880 which further up-regulates autophagy. Both loc146880 and autophagy could promote lung tumor cell migration, invasion and EMT. In addition, a positive correlation was observed between loc146880 expression and lc3b levels in tumor tissues and serum of lung cancer patients. CONCLUSION: Taken together, our data suggest that PM2.5 exposure induces ROS, which activates loc146880 expression. The lncRNA, in turn, up-regulates autophagy and promotes the malignant behaviors of lung cancer cells. GENERAL SIGNIFICANCE: The results show the toxicological effects of PM2.5 in lung tumor progression and metastasis.