Lung cancer is the most common cause of death from cancer and is estimated to have been responsible for nearly one in five deaths (1.59 million deaths, 19.4% of the total) in 2012 worldwide. People have known that lung cancer is associated with environmental factors, and both cigarette smoke and air pollution are known to cause cancers in humans. However, how air pollution causes lung cancer remains largely unknown.
Xuanwei City in China is suited to the study of this question because until the 1970s its inhabitants used 'smoky coal' for cooking in unventilated indoor spaces; this produced high levels of small particles that contain high concentrations of polycyclic aromatic hydrocarbon (PAHs) which can cause cancers in humans and animals. Women from this region, who traditionally do most of the cooking, have rates of lung cancer comparable to those of men. In other parts of China a woman’s chance of getting lung cancer is approximately half that of a man’s. Therefore, Xuanwei City provides a setting in which air pollution is a main contributor to lung cancer risk.
Prof Guang-Biao Zhou and colleagues have been investigating how air pollution induces lung cancer using Xuanwei lung cancer as a model. They showed that the ambient particulate matter can induce alterations in the genome, microRNAs (miRNAs, 19-25 nucleotides in length), and inflammation factors. Recently, they studied the roles of long non-coding RNAs (lncRNAs; more than 200 nucleotides in length) in air pollution-induced lung cancer by using Xuanwei lung cancer specimens and a human lncRNA microarray containing 33045 lncRNAs and 30215 mRNAs. They reported that Xuanwei patients had much more dysregulated lncRNAs and mRNAs than patients from control regions where pollution was similar to national averages. The lncRNA CAR intergenic 10 (CAR10) was elevated in 39/62 (62.9%) of the Xuanwei patients, which was much higher than in patients from control regions (32/86, 37.2%; p=0.002). A multivariate regression analysis showed an association between CAR10 overexpression and air pollution, and a PAH carcinogen dibenz[a,h]anthracene induced CAR10 by increasing the expression of a transcription factor called FoxF2. CAR10 bound and stabilized transcription factor Y-box-binding protein 1 (YB-1), leading to up-regulation of the oncoprotein epidermal growth factor receptor (EGFR).
Importantly, CAR10 promoted lung cancer cell growth at cellular and animal models. Silencing of CAR10 inhibited cancer growth at cellular models and suppressed tumor progression in mice harboring lung cancer cells. These results demonstrate the role of lncRNAs in environmental lung carcinogenesis, and CAR10-YB-1 represents a potential therapeutic target. CAR10 may also have potentials in prediction of lung cancer risk in residents of air polluted regions.