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:ObjectiveLung cancer is a leading cause of cancer death in the United States. Exposure to outdoor air pollution (OAP) is associated with increased lung cancer incidence, however little is known about the association of OAP and survival after diagnosis.MethodsWe investigated the effects of OAP and lung cancer survival in Pennsylvania using data from Pennsylvania Cancer Registry. The study population consisted of 252,123 patients diagnosed between 1990 and 2017. The Environmental Protection Agency's ambient air monitoring network provided information on OAP exposure of NO2, O3, PM2.5, and PM10. Mean OAP exposures were calculated by interpolating exposure concentrations from the five nearest monitors within a 50-kilometer radius of each patient's residential address from date of diagnosis to date of death or last contact. Cox proportional-hazards models were used to estimate the hazard ratios (HR) for OAP exposures for overall and lung cancer-specific survival. Statistical analyses were stratified by SEER cancer stage groupings (localized, regional, and distant) and adjusted for individual-level and area-level covariates.ResultsMedian survival time was 0.76 [CIs: 0.75, 0.77] years for the study population and for localized, regional, and distant site diagnosis were 2.2 [CIs: 2.17, 2.23], 1.13 [CIs: 1.12, 1.15], and 0.42 [CIs: 0.41, 0.43] years, respectively. NO2 indicated the greatest HR which increased with increasing magnitude of exposure across all cancer staging groups for deaths before 2-years post-diagnosis. HRs varied by stage and magnitude of OAP exposure with greatest overall effects shown in NO2 followed by PM2.5, O3, and PM10. A subgroup analysis of patients with treatment status information (2010-2017) showed similar associations of increasing HRs with increasing exposure.ConclusionThese findings supported the hypotheses that OAP can influence the carcinogenic process, impairing chemotherapy treatment, and provide important public health implications since environmental factors are not often considered in prognosis of survival after diagnosis.

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.

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.

Dataset Information

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

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

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