Cancer stem cells (CSC) are believed to play a central role in oncogenesis, but until todaytheir isolation and characterization is still particularly complex. Anaplastic thyroid cancer(ATC) presents several characteristics suggestive of a tumour highly enriched in CSC (highmitotic rate, poor prognosis, high aggressiveness, resistance to treatments, etc). For thesereasons ATC represents a good candidate to study CSCs. SOX2 is a key stemtranscriptional factor, usually only transiently expressed, that plays a fundamental role instem cell identity. SOX2 proved to be constitutively expressed in SW1736 cell line, a wellestablished and recognized ATC cell line. The bioinformatics ceRNA analysis permits todiscover gene transcripts that may be post-transcriptionally positively co-regulated withthe 3’UTR probe.We aimed to perform ceRNA analysis in SW1736 to identify candidate genes that might beinvolved in SOX2 functional network and in turn in stemness and CSC biogenesis. Acompeting endogenous RNA (ceRNA) in silico analysis was performed on 3’UTR of SOX2mRNA. Our analysis harvested several genes involved in the RNA interference mechanism(DICER1, DROSHA, AGO2) and in cell cycle control (TP53, CCND1). To further validatethe in silico analysis, in vitro analysis via RT-PCR was performed. Knocking down SOX2in SW1736 (0.417 expression rate), the interacting ceRNA transcripts were coherentlydownregulated with significant differences (expression rates from 0.355 to 0.705, p <0.05). Moreover, a statistical analysis of the ceRNAs in other cell lines and clinicalspecimens revealed a positive correlation with the expression of TP53, DICER1, DROSHAand AGO2, suggesting the existence of a fine regulatory network.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2013|