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

Tobias Ackermann; Gotz Hartleben; Christine Mueller; Guido Mastrobuoni; Marco Groth; Britt A. Sterken; Mohamad A. Zaini; Sameh A. Youssefi; Hidde R. Zuidhof; Sara R. Krauss; Gertrud Kortman; Gerald de Haan; Alain de Bruin; Zhao-Qi Wang; Matthias Platzer; Stefan Kempa; Cornelis F. Calkhoven

doi:10.1038/s42003-019-0461-z

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

Tobias Ackermann, Gotz Hartleben, Christine Mueller, Guido Mastrobuoni, Marco Groth, Britt A. Sterken, Mohamad A. Zaini, Sameh A. Youssefi, Hidde R. Zuidhof, Sara R. Krauss, Gertrud Kortman, Gerald de Haan, Alain de Bruin, Zhao-Qi Wang, Matthias Platzer, Stefan Kempa, Cornelis F. Calkhoven^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	208
Number of pages	15
Journal	Communications biology
Volume	2
DOIs	https://doi.org/10.1038/s42003-019-0461-z
Publication status	Published - 14-Jun-2019

Keywords

BINDING-PROTEIN-BETA
TRANSCRIPTION FACTORS
BREAST-CANCER
TRANSLATIONAL CONTROL
INHIBITORY PROTEIN
GENE-EXPRESSION
MICRORNA LET-7
MESSENGER-RNA
IN-VIVO
LIN28B

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C/EBPβ-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in miceFinal publisher's version, 2.04 MBLicence: CC BY

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Ackermann, T., Hartleben, G., Mueller, C., Mastrobuoni, G., Groth, M., Sterken, B. A., Zaini, M. A., Youssefi, S. A., Zuidhof, H. R., Krauss, S. R., Kortman, G., de Haan, G., de Bruin, A., Wang, Z.-Q., Platzer, M., Kempa, S., & Calkhoven, C. F. (2019). C/EBP beta-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice. Communications biology, 2, Article 208. https://doi.org/10.1038/s42003-019-0461-z

@article{04bdda9444f44dfc8b270538ed68732d,

title = "C/EBP beta-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice",

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 = "BINDING-PROTEIN-BETA, TRANSCRIPTION FACTORS, BREAST-CANCER, TRANSLATIONAL CONTROL, INHIBITORY PROTEIN, GENE-EXPRESSION, MICRORNA LET-7, MESSENGER-RNA, IN-VIVO, LIN28B",

author = "Tobias Ackermann and Gotz Hartleben and Christine Mueller and Guido Mastrobuoni and Marco Groth and Sterken, {Britt A.} and Zaini, {Mohamad A.} and Youssefi, {Sameh A.} and Zuidhof, {Hidde R.} and Krauss, {Sara R.} and Gertrud Kortman and {de Haan}, Gerald and {de Bruin}, Alain and Zhao-Qi Wang and Matthias Platzer and Stefan Kempa and Calkhoven, {Cornelis F.}",

year = "2019",

month = jun,

day = "14",

doi = "10.1038/s42003-019-0461-z",

language = "English",

volume = "2",

journal = "Communications biology",

issn = "2399-3642",

publisher = "Nature Publishing Group",

}

Ackermann, T, Hartleben, G, Mueller, C, Mastrobuoni, G, Groth, M, Sterken, BA, Zaini, MA, Youssefi, SA, Zuidhof, HR, Krauss, SR, Kortman, G, de Haan, G , de Bruin, A, Wang, Z-Q, Platzer, M, Kempa, S & Calkhoven, CF 2019, 'C/EBP beta-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice', Communications biology, vol. 2, 208. https://doi.org/10.1038/s42003-019-0461-z

TY - JOUR

T1 - C/EBP beta-LIP induces cancer-type metabolic reprogramming by regulating the let-7/LIN28B circuit in mice

AU - Ackermann, Tobias

AU - Hartleben, Gotz

AU - Mueller, Christine

AU - Mastrobuoni, Guido

AU - Groth, Marco

AU - Sterken, Britt A.

AU - Zaini, Mohamad A.

AU - Youssefi, Sameh A.

AU - Zuidhof, Hidde R.

AU - Krauss, Sara R.

AU - Kortman, Gertrud

AU - de Haan, Gerald

AU - de Bruin, Alain

AU - Wang, Zhao-Qi

AU - Platzer, Matthias

AU - Kempa, Stefan

AU - Calkhoven, Cornelis F.

PY - 2019/6/14

Y1 - 2019/6/14

N2 - 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.

AB - 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.

KW - BINDING-PROTEIN-BETA

KW - TRANSCRIPTION FACTORS

KW - BREAST-CANCER

KW - TRANSLATIONAL CONTROL

KW - INHIBITORY PROTEIN

KW - GENE-EXPRESSION

KW - MICRORNA LET-7

KW - MESSENGER-RNA

KW - IN-VIVO

KW - LIN28B

U2 - 10.1038/s42003-019-0461-z

DO - 10.1038/s42003-019-0461-z

M3 - Article

SN - 2399-3642

VL - 2

JO - Communications biology

JF - Communications biology

M1 - 208

ER -

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

Abstract

Keywords

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