Dataset Information

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.

SUBMITTER: Pan HL

PROVIDER: S-EPMC4585805 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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Down-regulation of microRNA-144 in air pollution-related lung cancer.

Pan Hong-Li HL Wen Zhe-Sheng ZS Huang Yun-Chao YC Cheng Xin X Wang Gui-Zhen GZ Zhou Yong-Chun YC Wang Zai-Yong ZY Guo Yong-Qing YQ Cao Yi Y Zhou Guang-Biao GB

Scientific reports 20150923

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 ...[more]

PMID: 26395400

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Project description:IntroductionCommuting exposes millions of people to carcinogens from traffic-related air pollution (TRAP) but is seldomly considered in epidemiologic studies of lung cancer. In the prospective United Kingdom (UK) Biobank cohort study, we investigated associations between commute patterns, residential nitrogen dioxide concentrations (NO2; a surrogate for TRAP), and lung cancer risk.MethodsWe analyzed 234,124 employed participants at baseline (2006-2010). There were 493 incident lung cancer cases diagnosed over an average 7-year follow-up. Subjects were cross-classified into exclusive categories of commute mode (automobile, public transportation, walking, cycling, active mixture, and other mixture) and frequency (regular: 1-4, often: ≥5 work-bound trips/week). Annual average residential NO2 concentrations in 2005-2007 were estimated with land use regression. Multivariable Cox regression was used to estimate associations between commute patterns, NO2 quartiles, and incident lung cancer. We conducted analyses stratified by NO2 (>, ≤median = 28.3 µg/m3) and potential confounders such as sex and smoking.ResultsCompared to regular automobile use, commuting often by public transportation was associated with increased lung cancer risk (hazard ratio (HR) = 1.58, 95% confidence intervals (CI):1.08-2.33). Additionally, we found a positive exposure-response relationship with residential NO2 (HRQ2 = 1.21, 95 %CI: 0.90-1.62; HRQ3 = 1.48, 95 %CI: 1.10-1.99; HRQ4 = 1.58, 95 %CI: 1.13-2.23; p-trend = 3.1 × 10-3). The public transportation association was observed among those with higher NO2 (p-interaction = 0.02). Other commute categories were not associated with risk.ConclusionsCommuters residing in high-NO2 areas who often use public transportation could have elevated lung cancer risk compared to regular automobile users. These results warrant investigations into which component(s) of public transportation contribute to the observed association with increased lung cancer risk.

Project description:Squamous cell lung cancer (SCC) and adenocarcinoma are the most common subtypes of the lung tumours. The search for cancer-directed treatments has increased the need for understanding molecular features of either histological subtype. The aim of this study was to identify transcriptional regulation differences due to miRNA expression profiles between SCC and adenocarcinoma. For this propose, a total of 44 patients were evaluated to assess the correlation between the miRNA and messenger RNA (mRNA) expression levels. Total RNA were isolated, amplified, labeled and hybridized on Agilent human whole genome V2 22 K microarray chip. qRT-PCR was conducted to validate our microarray data. MicroRNA expression was detected and quantified using the TaqMan Low Density Arrays. Predicted miRNA-mRNA interactions were taken from miRanda, miRWalk and TargetScan. After processing data, changes in 56 mRNAs as well as in 9 miRNAs were detected between SCC and adenocarcinoma. Nearly 20% of overall deregulated genes were targeted by at least one of the 9 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a, miR-483-5p, miR-494, miR-601 and miR-708) differentially expressed between SCC and adenocarcinoma. Genes predicted (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) to be targeted by several miRNAs were individually validated by qRT-PCR. We found genes involved in tight junctions and other involved in resistance to anticancer agents. These genes were reliable biomarkers, with high sensitivity and specificity, to detect differences between the two most common histological subtypes of lung cancer. In conclusion, our data demonstrate that the transcriptional regulation differences through miRNA expression play an important role in key hallmarks of non-small cell lung cancer. Identification of new molecular markers in lung carcinoma 44 tumour samples following surgical resection for clinical early stage NSCLC (SCC and adenocarcinoma) This series represents the mRNA profiling only (not miRNA). The related miRNA data are in Series GSE43000.

Dataset Information

Down-regulation of microRNA-144 in air pollution-related lung cancer.

Publications

Down-regulation of microRNA-144 in air pollution-related lung cancer.

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