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C/EBPβ-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice

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Item Type:Article
Title:C/EBPβ-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice
Creators Name:Ackermann, T. and Hartleben, G. and Müller, C. and Mastrobuoni, G. and Groth, M. and Sterken, B.A. and Zaini, M.A. and Youssef, S.A. and Zuidhof, H.R. and Krauss, S.R. and Kortman, G. and de Haan, G. and de Bruin, A. and Wang, Z.Q. and Platzer, M. and Kempa, S. and Calkhoven, C.F.
Abstract:The transcription factors LAP1, LAP2 and LIP are derived from the Cebpb-mRNA through the use of alternative start codons. High LIP expression has been associated with human cancer and increased cancer incidence in mice. However, how LIP contributes to cellular transformation is poorly understood. Here we present that LIP induces aerobic glycolysis and mitochondrial respiration reminiscent of cancer metabolism. We show that LIP-induced metabolic programming is dependent on the RNA-binding protein LIN28B, a translational regulator of glycolytic and mitochondrial enzymes with known oncogenic function. LIP activates LIN28B through repression of the let-7 microRNA family that targets the Lin28b-mRNA. Transgenic mice overexpressing LIP have reduced levels of let-7 and increased LIN28B expression, which is associated with metabolic reprogramming as shown in primary bone marrow cells, and with hyperplasia in the skin. This study establishes LIP as an inducer of cancer-type metabolic reprogramming and as a regulator of the let-7/LIN28B regulatory circuit.
Keywords:CCAAT-Enhancer-Binding Protein-beta, Carcinogenesis, Cell Proliferation, Codon, Fibroblasts, Glycolysis, HEK293 Cells, Knockout Mice, Messenger RNA, MicroRNAs, Mitochondria, Neoplasms, Neoplastic Cell Transformation, Oxygen Consumption, Proteome, RNA Interference, RNA-Binding Proteins, Signal Transduction, Transgenic Mice, Tumor Cell Line, Animals, Mice, Rats
Source:Communications Biology
Page Range:208
Date:14 June 2019
Official Publication:https://doi.org/10.1038/s42003-019-0461-z
PubMed:View item in PubMed

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