Protein-coding and non-coding gene expression analysis in differentiating human keratinocytes using a three-dimensional epidermal equivalent

The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and corniWed layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, diVerentiation, and cell death. To determine genes responsible for initiating and maintaining a corniWed epidermis, organotypic cultures comprised entirely of stratiWed KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array proWle of submerged cultures containing KCs predominantly in a proliferative (relatively undiVerentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct proWle of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, diVerentiation, and cell death. Next, diVerentially expressed microRNAs (miRNAs) and long noncoding (lncRNA) RNAs were identiWed in EEs. Several diVerentially expressed miRNAs were validated by qRT-PCR and Northern blots. miRNAs 203, 205 and Let-7b were up-regulated at early time points (6, 18 and 24 h) but downregulated by 120 h. To study the lncRNA regulation in EEs, we proWled lncRNA expression by microarray and validated the results by qRT-PCR. Although the diVerential expression of several lncRNAs is suggestive of a role in epidermal diVerentiation, their biological functions remain to be elucidated. The current studies lay the foundation for relevant model systems to address such fundamentally important biological aspects of epidermal structure and function in normal and diseased human skin

Discovering cancer genes by integrating network and functional properties

<p>Abstract</p> <p>Background</p> <p>Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI) data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO) annotations, to facilitate the identification of cancer genes.</p> <p>Methods</p> <p>Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1.</p> <p>Results</p> <p>Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs) with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1.</p> <p>Conclusion</p> <p>Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.</p

За кадры. 1965. № 19 (1100)

"Через века, через года - помните!"Экзамены приняли старт / В. АлександровНИИ физики твердого телаНаш V традиционный / В. Жмуренко, С. Савин, Д. ЦыремпиловНа конференции в НовосибирскеПартгруппа одной кафедры / Р. ХохловаУглубление знаний - основа культуры / С. ШварцевЭкзамены по физике / Л. КалачниковаО технической эстетике / О. УдодоваВажный фактор / Г. ПетроваЧастица добрых дел химиков / В. ХлыстунУ автоматчиков / Г. ВасильевСлово - гостям / Г. КостенкоСюрпризы спортсменов / Б. АфонинВпереди - встречи / А. ПетренкоДелитесь теплом / О. ФилософовВ общежитии / Т. НефедоваБерезы / В. ПетровСовременнику / В. ЧекалинО банальности / В. ИвановО поэзии наших дней / В. ИвановВ гостях у В. Иванова / В. ЗеленскийВесной в лес