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Impact of miRNA for the development of chromosomal instability and dedifferentiation in hepatocellular carcinoma

English title Impact of miRNA for the development of chromosomal instability and dedifferentiation in hepatocellular carcinoma
Applicant Wilkens Ludwig
Number 118065
Funding scheme Project funding (Div. I-III)
Research institution Nordstadtkrankenhaus Klinikum Region Hannover Pathologisches Institut für Pathologie
Institution of higher education University of Berne - BE
Main discipline Experimental Cancer Research
Start/End 01.11.2007 - 31.01.2011
Approved amount 227'000.00
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Keywords (3)

HCC; miRNA; chromosomale Instabilität

Lay Summary (English)

Lead
Lay summary
Chromosomal instability (CIN) is a characteristic feature of most solid tumours. A frequent tumour revealing CIN is hepatocellular carcinoma, the fourth most common carcinoma in the world. Typical chromosomal aberrations occuring as a consequence of CIN in HCC include gains for 1q 6p,8q and 17q as well as losses for 1p, 4q, 6q, 8p, 13q, 16q, and 17p, respectively. Of these losses 4q and 13q are correlated with morphological dedifferentiation of HCC. Morphological dedifferentiation and increasing CIN in HCC are also closely correlated together with distinct alterations in mRNA expression. Proliferation-related genes CMYC and E2F1 were upregulated in morphologically dedifferentiated HCC and associated with an increasing polyploidisation as proven by fluorescence in situ hybridisation (FISH). Morphological dedifferentiation and CIN are also associated with epigenetic factors of which the most important are DNA-methylation, histone-acetylation, and miRNA expression. Whereas efforts have already been made or are underway to analyse DNA-methylation and histone acetylation little is known about the correlation of morphological dedifferentiation and CIN in HCC with miRNA expression. Since recent reports explain the regulation of proliferation genes CMYC and E2F1 by miRNAs miR-17-5p and miR20-a, and miRNA may have a major impact in malignomas such as chronic lymphatic leukaemia, alterations of miRNA expression could likely also be involved in morphological and genetic dedifferentiation of HCC. The purpose of this study is therefore to analyse miRNA in morphologically dedifferentiated HCC. In particular it is the aim of this study to look for a correlation of the expression of miRNA localized on chromosome regions frequently altered in HCC, i.e. 4q, 8q, and 13q, respectively with additional genetic imbalances and changes of the mRNA profile occurring in these cases.
Direct link to Lay Summary Last update: 21.02.2013

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