Inhalation of carcinogenic PM2.5 particles is a severe threat to all the people in both developing and developed nations. However, which components of PM2.5 and how they perturb human cells to cause various diseases are still not understood. Here, employing a reductionism approach, we revealed that one of the crucial toxic and pathogenic mechanisms of PM2.5 was the blocking of human bronchial cell cycle through upregulation of a novel long non-coding RNA NONHSAT074301.2 by carbon particles with payloads of Cr(VI) and Pb2+. We also discovered that NONHSAT074301.2 is a key regulatory molecule controlling cell cycle arrest at G2/M phase. This work highlights cellular function and molecular signaling events investigations using a 16-membered combinational model PM2.5 library which contain carbon particles carrying four toxic pollutants in all possible combinations at environmental relevant concentrations. This work demonstrates a very powerful methodology to elucidate mechanisms at molecular level and help unlock the "black box" of PM2.5-induced toxicities.
Keywords: Causal effect; Combinatorial library; Mechanistic toxicity; Noncoding RNA; Synergistic effects.
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