Page 80 - ebook HCC

78 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 79
FEBRUARY 13 - 16, 2014

MICRO RNA

Laura Gramantieri 1
1 S.Orsola-Malpighi University Hospital, Bologna, Italy
Corresponding author’s e-mail: laura.gramantieri@aosp.bo.it

The critical role of microRNAs (miRNAs) in tumorigenesis has been widely investigated Proteins regulating cell cycle progression, apoptosis, senescence, EMT, cell migration and
and ascertained in the last decade, confirming their important regulatory action in several invasion capability were identified among the targets of deregulated miRNAs. Remarkably,
biological processes involved in cancer development and progression. MiRNAs constitute in vitro findings should be interpreted keeping in mind that such experimental conditions
a large class of genes that encode short RNAs (19-24 nucleotides long), which play key are very outstretched, and that cell and tissue context play a fundamental role in the
roles in development and differentiation, by the post-transcriptional regulation of protein determination of miRNA functions. In addition, the microenvironment surrounding tumor
coding genes. At present, miRNAs have a widely recognized role in human carcinogenesis, tissue was demonstrated to play an important role as well. From a translational point of
including hepatocarcinogenesis, and many experimental evidences indicate that they may
BASIC SPEAKERS ABSTRACTS coding genes. By binding to complementary sequences in the 3’UTR of target genes, these findings still need an adequate validation. Since miRNAs are biomarkers with BASIC SPEAKERS ABSTRACTS
view, miRNAs have been proposed as possible novel biomarkers for cancer diagnosis,
act as oncogenes or tumor suppressor genes regulating the expression of crucial protein-
prognostic assessment and assessment of susceptibility to different treatments. However
miRNAs can promote their degradation or impair their translation. Interestingly, miRNAs
beknown potential in molecular classification and prognostication in HCC tissue, they
display their effects also on mRNAs with a partial sequence complementarity. Therefore,
are being the more and more addressed as possible biomarkers to be assayed also in
body fluids, such as serum, plasma and urine. Despite several studies appeared in the
one miRNA may modulate the expression of a wide range of mRNAs at one time, thus
literature in the last years, still no common pattern has been found on circulating miRNAs
regulating more pathways or one pathway at more levels. Thus, a fine modulation on
single mRNAs may produce relevant final effects. MiRNA-based molecular signatures
characterize different tumor types, including HCC and, despite some discrepancies
reasons, including different study designs, analytical approaches, heterogeneous internal
and exogenous standards, different populations enrolled as controls. The understanding
can be found through the different series reported in the literature, a panel of miRNAs deregulated in HCC. The wide heterogeneity of such studies should be ascribed to several
commonly deregulated in HCC can be identified. Among these commonly deregulated of HCC pathogenesis could be an opportunity to develop new targeted strategies and
miRNAs in HCC tissue, miR-21, miR-199, miR-221 and miR-122, are recurrent and seem therapeutic approaches against HCC. MiRNAs modulation represents an appealing
to characterize HCC tissue regardless of etiology of the underlying liver disease. Yet, treatment modality for liver diseases, due to the high uptake of these kind of molecules by
deregulated miRNAs signatures may also help to identify HCCs with different etiology, the liver itself, after peripheral vein injection. In addition, no relevant adverse event was
genetic background and prognosis. Interestingly, miRNA signatures have been proposed reported after miRNA-based therapeutic approach against HCV infection. We have recently
to complement transcriptomic signatures in several malignant diseases including HCC. reported that anti-miR-221 has a significant antitumor activity in a TG-221 transgenic
Molecular events driving miRNAs expression are still poorly understood, however mouse model over-expressing miR-221 in the liver. Histo-pathological analyses showed a
evidences are accumulating on the role of transcription factors and epigenetic changes. significant reduction in the number and size of tumors of treated mice in comparison with
In addition, miRNA mutations have also been described in neoplastic tissues, possibly untreated animals and at the molecular level a significant down-regulation of miR-221 in
associated with their abnormal expression and function. Regulatory feed-back or feed- liver of anti-miR-221 treated mice was displayed, confirming the ability of these molecules
forward loops have also been identified, contributing to the deregulated expression of to inhibit the endogenous miR-221. While pre-clinical studies in in vivo models of HCC
miRNAs in several malignancies.The understanding of miRNAs contribute to the malignant seem to confirm the great potential of miRNAs as therapeutic targets, yet we should keep
phenotype has been attempted by the identification of their target genes. Several gene in mind the context-dependent role of miRNAs as well as their possible action at distant
products playing relevant roles in the malignant phenotype have been identified as miRNA sites and off target effects.
targets, mainly by using in vitro approaches.