title: Down-regulation of microRNA-144 in air pollution-related lung cancer.
abstract: Air pollution has been classified as a group 1 carcinogen in humans, but the underlying tumourigenic mechanisms remain unclear. In Xuanwei city of Yunnan Province, the lung cancer incidence is among the highest in China, owing to severe air pollution generated by the combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis. To identify abnormal miRNAs critical for air pollution-related tumourigenesis, we performed microRNA microarray analysis in 6 Xuanwei non-small cell lung cancers (NSCLCs) and 4 NSCLCs from control regions where smoky coal was not used. We found 13 down-regulated and 2 up-regulated miRNAs in Xuanwei NSCLCs. Among them, miR-144 was one of the most significantly down-regulated miRNAs. The expanded experiments showed that miR-144 was down-regulated in 45/51 (88.2%) Xuanwei NSCLCs and 34/54 (63%) control region NSCLCs (p = 0.016). MiR-144 interacted with the oncogene Zeb1 at 2 sites in its 3' untranslated region, and a decrease in miR-144 resulted in increased Zeb1 expression and an epithelial mesenchymal transition phenotype. Ectopic expression of miR-144 suppressed NSCLCs in vitro and in vivo by targeting Zeb1. These results indicate that down-regulation of miR-144 is critical for air pollution-related lung cancer, and the miR-144-Zeb1 signalling pathway could represent a potential therapeutic target.
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences &Graduate School of the University of Chinese Academy of Sciences, Beijing 100101.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Pan
authors.affiliation: Department of Thoracic Surgery, the Cancer Hospital, Sun Yat-Sen University, Guangzhou 510060.
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Wen
authors.affiliation: Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming 650106, China.
authors.forename: Yun-Chao
authors.initials: YC
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences &Graduate School of the University of Chinese Academy of Sciences, Beijing 100101.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences &Graduate School of the University of Chinese Academy of Sciences, Beijing 100101.
authors.forename: Gui-Zhen
authors.initials: GZ
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming 650106, China.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029.
authors.forename: Zai-Yong
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Guo
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences &Graduate School of the University of Chinese Academy of Sciences, Beijing 100101.
authors.forename: Guang-Biao
authors.initials: GB
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002681:China; D018450:Disease Progression; D015536:Down-Regulation; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics; D012906:Smoke / Q000009:adverse effects; D014157:Transcription Factors / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; C554293:MIRN144 microRNA, human; D035683:MicroRNAs; D012906:Smoke; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1