Maturazione dei microRNA: effetto sulla regolazione dell'espressione genica nell'epatocancerogenesi umana

Aim: microRNAs (miRNAs),short (19-25 nt),endogenus, non-coding, single-stranded RNA molecules, are able to regulate gene expression at post-transcriptional level by binding to 3’-UTR or 5’-UTR or coding region. miRNAs are usually transcribed, in nucleus, by RNA polymerase II (and some by RNA polymerase III) as long primary immature miRNAs (pri-miRNAs). The pri-miRNAs are cleaved in short transcripts,the pre-miRNA (100 bp),by a complex called Microprocessor formed by Drosha and DGCR8. The pre-miRNAs (70-110 nt) are therefore exported into the cytoplasm by Exportin-5,where they are further processed by Dicer in mature miRNA (20-25 nt). Only single strand of the mature miRNA is incorporated into the RISC complex involved in gene silencing. miRNAs play an important role in the proliferation, differentiation, migration, apoptosis, control of the cell cycle and cell metabolisms through modulating mRNA stability. miRNAs may play a role in human diseases,for example tumors as hepatocellular carcinoma (HCC). It’s important therefore to study the expression of genes involved in miRNA synthesis and maturation (Drosha,DGCR8,Exportin-5 and Dicer). Methods: We use normal and cancer liver tissues from patients who have given their consensus. We analyzed histo-patologically liver cancer samples from HCC tissues and in the corresponding adjacent noncancerous liver tissues. We performed real time qRT-PCR to evaluate and quantify the expression of Drosha, DGCR8, Exportin-5 and Dicer genes. Results: We found that Drosha,DGCR8, exportin-5 and Dicer were up-regulated in all neoplastic tissue samples tested, compared to normal value. Conclusions: Our results suggest that Drosha, DGCR8, Exportin-5 and Dicer could be involved directly or indirectly in the development of HCC or in its progression