Page 99 - ebook HCC

EASL
PROGRAMME AND ABSTRACTSAND ABSTRACTS
GENEV
97
96 PROGRAMME GENEVA, SWITZERLANDA, SWITZERLAND EASL HCC SUMMITHCC SUMMIT 97
96
FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
FEBRUAR
Poster Board Number B5
HARNESSING THE THERAPEUTIC POTENTIAL OF
MICRORNAS INVOLVED IN THE PROGRESSION
AND REGRESSION OF HEPATOCELLULAR
CARCINOMA

Asha Balakrishnan , Andrei Goga , Michael P. Manns , Michael Ott 1 2 Results: We find that in addition to differential regulation of global miRNA pathways during
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1 Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, liver tumor development and regression, the four different groups analyzed also show
2 Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany, significantly distinct microRNA expression patterns and segregate separately. Based on
3 Department of Cell & Tissue Biology, Department of Medicine, University of California, >2-fold differential regulation and a p<0.05, we identified potential tumor inhibitory or
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San Francisco, San Francisco, United States promoting miRNAs that were differentially regulated between the full-blown tumors and
those in the regression time point.
Corresponding author’s e-mail: balakrishnan.asha@mh-hannover.de
Conclusions: Functional validation of these selected miRNAs further indicate that miRNAs
deregulated during HCC progression as well as when HCC tumors start to regress may
Introduction: Hepatocellular carcinoma (HCC), the most common type of liver cancer, is play significant roles in these processes. The discovery of novel miRNA-based biomarkers
amongst the top three leading causes of cancer-related deaths worldwide with a median and therapeutic targets is crucial for the development of novel therapeutic options for this
currently intractable disease.
survival of only six to eight months. HCCs are refractory to most existing therapeutics;
BASIC POSTER ABSTRACTS hepatocytes to readily take-up nucleic acids raises the hope that small nucleic acid-based BASIC POSTER ABSTRACTS
therefore, novel and more effective treatments need to be developed. The propensity of
drugs may have utility against liver cancer. Small non-coding microRNAs (miRNAs) are
one such class of nucleic acids that are emerging as promising therapeutic targets in
cancers. MiRNAs affect a wide range of cellular functions including growth, differentiation,
and death, and are deregulated in many human cancers including HCCs. Whether
miRNAs may affect tumor regression and the corresponding underlying mechanisms have
not been addressed.

Aims:
1. To identify novel microRNAs involved in HCC progression and regression by microRNA
expression profiling.
2. To study the effect of significantly and differentially expressed candidate miRNAs in
HCC.

Methodology: We have used liver samples collected from a conditional doxycycline-
regulated c-MYC-driven liver tumor model at four specific stages – non-tumor, early
stage pre-tumor livers, full-blown liver tumors and regressing liver tumors – to carry out
miRNA profiling. This was followed by in-depth in silico analyses to identify significantly
deregulated and differentially expressed miRNAs that are altered during specific stages of
tumor progression and as tumors regress.