Human hepatocellular carcinoma cell-specific miRNAs reveal the differential expression of miR-24 and miR-27a in cirrhotic/non-cirrhotic HCC

Abstract. microRNAs (miRs) are 18-25 nucleotide non-coding
RNAs that regulate gene expression in several physiological
and pathological conditions. To gather more knowledge on
microRNAs in human hepatocellular carcinoma (HCC) we
generated a small RNA library in the human HCC cell line
HA22T/VGH by cloning and sequencing the cDNA obtained
following the size selection of 18-24 nucleotide RNAs. We
determined the expression levels of the most frequently cloned
microRNAs by qPCR in HCC tissues and in their peritumoral
counterparts from biopsy specimens of 41 HCC patients.
The most frequently cloned miRs were miR-24, miR-27a and
miR-21, and their expression levels in human HCC tissues indicate
that these miRs were dysregulated in HCC. We showed
that miR-24 and miR-27a were significantly downregulated in
HCCs from cirrhotic liver tissues in comparison to those from
non-cirrhotic liver tissues. In cirrhotic HCCs the downregulation
of miR-24 was correlated with poorer prognosis in patients
with HBV and HCV virus infections. miR-21 was generally
upregulated in HCC tissues versus the corresponding peritumoral
tissues, particularly in non-cirrhotic HCC. Furthermore,
by sequence alignment we identified the human miR orthologue
of Mus musculus miR-1199 not yet annotated. Our
results outline the differential expression of miRs in cirrhotic
and non-cirrhotic HCCs, thereby contributing to advances in
the discovery and validation of novel molecular biomarkers of HCC progression.