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lncRNA HOTTIP / HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients

Quagliata, L. and Matter, M. S. and Piscuoglio, S. and Arabi, L. and Ruiz, C. and Procino, A. and Kovac, M. and Moretti, F. and Makowska, Z. and Boldanova, T. and Andersen, J. B. and Hammerle, M. and Tornillo, L. and Heim, M. H. and Diederichs, S. and Cillo, C. and Terracciano, L. M.. (2014) lncRNA HOTTIP / HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology, Vol. 59, No. 3. pp. 911-923.

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Official URL: http://edoc.unibas.ch/dok/A6338549

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Abstract

Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death. Despite the advances in diagnosis and management of HCC, the biology of this tumor remains poorly understood. Recent evidence highlighted long non-coding RNAs (lncRNAs) as crucial determinants of HCC development. In this study, we report the lncRNA HOTTIP as significantly up-regulated in HCC specimens. HOTTIP gene is located in physical contiguity with HOXA13 and directly controls the HOXA locus gene expression via interaction with the WDR5 / MLL complex. HOX genes encode transcription factors regulating embryonic development and cell fate. We previously described HOX genes deregulation to be involved in hepatocarcinogenesis. Indeed, we observed the marked up-regulation of HOXA13 in HCC. Here, by correlating clinico-pathological and expression data, we demonstrate that the levels of HOTTIP and HOXA13 are associated with HCC patients' clinical progression and predict disease outcome. In contrast to the majority of similar studies, our data are obtained from snap-frozen needle HCC biopsies (n=52) matched with their non-neoplastic counterparts collected from patients that had not yet received any HCC-tailored therapeutic treatments at the time of biopsy. In addition, taking advantage of gain and loss of function experiments in liver cancer-derived cell lines (HuH-6 and HuH-7), we uncover a novel bidirectional regulatory loop between HOTTIP / HOXA13. Conclusion: our study highlights the key role of HOTTIP and HOXA13 in HCC development by associating their expression to metastasis and survival in HCC patients, provides novel insights on the function of lncRNA-driven hepatocarcinogenesis and paves the way for further investigation about the possible role of HOTTIP as predictive biomarker of HCC. (Hepatology 2013;).
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Saunders
ISSN:0270-9139
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Mar 2015 07:44
Deposited On:06 Mar 2015 07:44

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