e14699 Background: The AP-1 transcription factor is a heterodimeric protein, which regulates gene expression in response to a variety of stimuli. The above factor also regulates cellular processes including differentiation, proliferation and apoptosis. The AP-1 heterodimeric protein is consisted of the combination of c-Jun and c-Fos proteins. The c-Jun is activated through phosphorylation, but it has also phosphorylation independent function. The c-FOS is a cellular proto-oncogene, which is up-regulated in response to many extracellular signals. The present study aim to find out the effect of c-FOS gene in Colon CSCs according to stemness. Methods: In all experiments there have been used established human colon cancer stem cells (CelProgen). Experiments for suppression of c-FOS expression, by using specific siRNA were performed and the transfection was evaluated with qPCR assays. The stemness transcription factors Nanog, Oct3/4 and Sox2 were tested with gene expression assays, and a relative quantification was performed according to Livak method. The CD44 and CD26 genes were used as positive markers in colon cancer in all procedures. Results: The results indicated that the c-FOS proto-oncogene affects the gene expression of transcription factors, which are essential for the maintenance of stemness. However the results were different, depending on the rate of suppression. The suppression of c-FOS by 65% led to increase in gene expression of stemness transcription factors, with higher rates for Nanog, smaller for Sox2 and minimum for Oct3/4. Unlike results were observed when the expression was suppressed by 85%. In this case there was observed higher decrease in Oct3/4 and less in the other markers. Conclusions: Up to now studies have demonstrated the significant role of c-JUN in stem cells, but little is known about the other half of AP-1 complex, the c-FOS gene. In the first part of the study it was confirmed the effect of c-FOS in stemness, as it was observed change in gene expression of stemness’s significant transcription factors. However it is indicated that there is a cross-talk between JNK pathway and stemness. Further studies in more samples are needed to demonstrate all the above, so that it can be used at clinical level.
Portulaca oleracea extract can inhibit nodule formation of colon cancer stem cells by regulating gene expression of the Notch signal transduction pathway
