Page 149 - ebook HCC

PROGRAMME
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EASL
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146 PROGRAMME AND ABSTRACTSAND ABSTRACTS GENEVA, SWITZERLANDA, SWITZERLAND EASL HCC SUMMITHCC SUMMIT 147
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FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
FEBRUAR
Poster Board Number B36 Poster Board Number B37
MITOTIC KINESIN-LIKE PROTEIN 2 MICRORNA EXPRESSION PATTERN IN
DEREGULATION IN HEPATOCELLULAR PBMCS FROM PATIENTS WITH HCV-RELATED
CARCINOMA MALIGNANCIES

Florence Bourgain , Mathieu Boissan , Dominique Wendum , Joelle Sobczak-Thepot 1 Alessia Piluso , Elisa Fognani , Laura Gragnani , Elena Grandini ,
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1 Biology and Therapy of Hepato-Biliary Tumors, UPMC - Saint-Antoine Research Center Monica Monti , Barbara Boldrini , Teresa Urraro , Mauro Bernardi ,
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- Inserm UMRS_938, Paris, France Giacomo Laffi , Pietro Andreone , Anna L. Zignego 1
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1 Experimental and Clinical Medicine, University of Florence, Florence,
Corresponding author’s e-mail: joelle.sobczak@inserm.fr 2 Department of Clinical Medicine, University of Bologna, Bologna, Italy
Corresponding author’s e-mail: lauragragnani@yahoo.it
Introduction: Mitotic kinesin-like protein 2 (MKlp2) is a plus-end microtubule-associated
motor required during mitosis exit for the final step of cytokinesis. It also contributes
to retrograde vesicular trafficking from the Golgi to the endoplasmic reticulum in Introduction: Hepatocellular carcinoma (HCC) is a major malignancy worldwide and is
interphase. We recently investigated the expression pattern of MKlp2 in normal liver and closely associated with HCV infection. Besides HCC, HCV is involved in the pathogenesis
hepatocellular carcinomas (HCCs). We observed a dramatic accumulation of MKlp2 in of non-Hodgkin’s lymphoma (NHL). HCV is the only virus infecting humans, able to induce
normal proliferating, preneoplastic and transformed hepatocytes suggesting that MKlp2 two different malignancies.
contributes to both normal and pathological hepatocyte proliferation. In addition MKlp2 We previously showed a down-regulation of miR-26b in peripheral blood mononuclear
overexpression was linked to tumor aggressiveness and genomic instability in human cells (PBMCs) from patients with HCV-related mixed cryoglobulinemia (MC) or NHL, and
BASIC POSTER ABSTRACTS Aims: The purpose of this study was to determine whether down regulation and Aims: The comparative analysis of miRNA expression between the two malignancies BASIC POSTER ABSTRACTS
an up-regulation of miR-16, miR-21 and miR-155 in NHL patients.
HCCs.
could provide some hints on the issue of differential evolution of HCV infection to HCC or
pharmacological inhibition of MKlp2 inhibited cell proliferation in vitro and in vivo.
NHL, suggesting the existence of common or distinct pathogenetic pathways and identify
Methodology: HuH6 human hepatoma cells were either treated with paprotrain, a
specific MKlp2 inhibitor, or transfected to constitutively express the KIF20A Sh-RNA. Cell
proliferation was quantified by MTT and clonogenic assays. Ploidy was determined by flow new useful biomarkers.
Methodology: We analyzed the expression of a panel of microRNAs in PBMCs from HCV
cytometric analysis of DNA contents. Tumorigenicity was determined after sub-cutaneous patients with or without HCC.
injection of 10 cells in Nude mice.
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Results: Results showed the up-regulation of miR-21 and down-regulation of miR-26b in
Results: We show here that both RNAi-mediated MKlp2 knockdown and pharmacological HCC patients compared to controls (p<0.001). MiR-146 levels were comparable in patients
inhibition of MKlp2 with paprotrain induced polyploidisation and inhibited cell proliferation. and controls. The expression of miR-16 and miR-155 did not differ in HCC patients and
In addition, RNAi-mediated MKlp2 knockdown inhibited tumorigenesis in the Nude mouse controls, indicating that their deregulated expression was limited to NHL patients.
model.
Conclusions: In conclusion, this study shows that some microRNA are differently
Conclusions: These data support that MKlp2 is a candidate therapeutic target in modulated in PBMCs from HCV patients who developed HCC or NHL, while others
hepatocellular carcinoma. follow a common behavior. Thus, microRNAs could represent non-invasive markers of
HCV-related cancerogenesis, useful to identify the existence of a malignancy and also to
discriminate between the two major HCV-related cancers.