Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients. We collected peripheral airway brushings from the contral-lateral lung of the tumor from cancer patients (n=17) and smoker controls (n=13); Total RNA were obtained from the peripheral airway epithelium.
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients. We collected peripheral airway brushings from the contral-lateral lung of the tumor from cancer patients (n=17) and smoker controls (n=13); Total RNA were obtained from the peripheral airway epithelium.
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.
Project description:Field of cancerization in the airway epithelium has been increasing examined to understand early pathogenesis of non-small cell lung cancer. This study uses microarray high-throughput technologies to characterize the molecular aberrations in the terminal airway and bronchoalveolar cells in the context of field cancerization in high-risk smokers and lung cancer patients.
Project description:Previous work has shown that lung tumors and normal-appearing adjacent lung tissues share specific abnormalities that may be highly pertinent to the pathogenesis of lung cancer. However, the global and molecular adjacent airway field cancerization in non-small cell lung cancer (NSCLC) has not been characterized before. We sought to understand the transcriptomic architecture of the adjacent airway field canerization, in conjunction with tumors, to gain additional insights into the lung cancer biology and oncogenesis. We analyzed the transcriptome, using the Affymetrix Human Gene 1.0 ST platform, of matched NSCLC tumors, multiple normal airway epithelia with differential distance from the tumors as well as uninvolved normal lung tissues. We analyzed the airway field cancerization transcritpome to determine global differentially expressed cancerization profiles in adjacent airways as well as airway profiles that may be modulated by distance from tumors.
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes