Long non-coding RNA stabilizes the Y-box-binding protein 1 and regulates the epidermal growth factor receptor to promote lung carcinogenesis

// Ming-Ming Wei 1, * , Yong-Chun Zhou 2, * , Zhe-Sheng Wen 3, * , Bo Zhou 1, * , Yun-Chao Huang 2 , Gui-Zhen Wang 1 , Xin-Chun Zhao 1 , Hong-Li Pan 1 , Li-Wei Qu 1 , Jian Zhang 1 , Chen Zhang 1 , Xin Cheng 1 , Guang-Biao Zhou 1 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China 2 Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming 650106, China 3 Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University, Guangzhou 510060, China * These authors have contributed equally to this work Correspondence to: Guang-Biao Zhou, email: gbzhou@ioz.ac.cn Keywords: air pollution, lung cancer, lncRNA CAR intergenic 10, YB-1, EGFR Received: April 04, 2016 Accepted: May 29, 2016 Published: June 14, 2016 ABSTRACT Indoor and outdoor air pollution has been classified as group I carcinogen in humans, but the underlying tumorigenesis remains unclear. Here, we screened for abnormal long noncoding RNAs (lncRNAs) in lung cancers from patients living in Xuanwei city which has the highest lung cancer incidence in China due to smoky coal combustion-generated air pollution. We reported that Xuanwei patients had much more dysregulated lncRNAs than patients from control regions where smoky coal was not used. The lncRNA CAR intergenic 10 ( CAR10 ) was up-regulated 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 smoky coal combustion-generated carcinogen dibenz[a,h]anthracene up-regulated CAR10 by increasing transcription factor FoxF2 expression. CAR10 bound and stabilized transcription factor Y-box-binding protein 1 (YB-1), leading to up-regulation of the epidermal growth factor receptor (EGFR) and proliferation of lung cancer cells. Knockdown of CAR10 inhibited cell growth in vitro and tumor growth in vivo. These results demonstrate the role of lncRNAs in environmental lung carcinogenesis, and CAR10 -YB-1 represents a potential therapeutic target.