The regulatory link between the transcription factor HNF4alpha and miRNA: Implication for the HNF4alpha mediated control of cell proliferation

• Applicant: Professor Dr. Gerhart U. Ryffel
• Subject Area: Cell Biology
• Term: from 2006 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 31639617

The tissue specific transcription factor HNF4¿ that is down-regulated in renal cell carcinoma inhibits cell proliferation and changes the cell morphology. We have established an embryonic human kidney cell line containing a single copy of the HNF4¿ gene that can be activated by doxycycline allowing a dose dependent inhibition of cell proliferation and change in cell morphology. By gene expression profiling we have identified the protein coding genes that are either up- or down-regulated by HNF4¿. By RNA interference we now screen for those genes that mediate the phenotypic effect of HNF4¿ to define the HNF4¿ mediated pathways controlling cell proliferation and cell morphology. We also want to identify among the miRNA genes, a novel type of gene regulators, those that are regulated by HNF4¿ to get insight into the link between a classical gene regulator, a well defined transcription factor, and these new regulatory molecules. In a complementary approach we will identify the miRNAs that target the 3´untranslated region of the HNF4¿ mRNA and thus regulate the level of the HNF4¿ transcription factor. Any miRNA that interacts with the HNF4¿ mRNA is likely to regulate cell proliferation and cell morphology and this will be verified experimentally.

• DFG Programme: Research Grants
• Participating Person: Privatdozent Dr. Ludger Klein-Hitpass, Ph.D.