PXD010095

PXD010095 is an original dataset announced via ProteomeXchange.

Title	C/EBPβ-LIP regulates the let-7/Lin28b circuit to induce cancer-type metabolic reprogramming
Description	The RNA binding protein Lin28b is highly expressed during embryogenesis but its expression declines in adult tissues, and aberrant expression of Lin28b is associated with tumour development and maintenance. Lin28b regulates the translation of several glycolytic and mitochondrial enzymes in order to enhance cellular metabolism and energy production. Lin28b is repressed by let-7 family microRNAs in a reciprocal negative regulatory circuitry where Lin28b supresses maturation of let-7. This circuitry obtains input from master regulators such as MYC that transcriptionally upregulates Lin28b, which is required for let-7 suppression and proliferation. Not much is known of how this circuitry is regulated through transcription of the let-7 microRNAs. Here we show that the transcription factor C/EBPβ-LIP induces aerobic glycolysis and mitochondrial respiration reminiscent to cancer cell metabolism. By integrating transcriptome, proteome and metabolic flux analysis we reveal that this LIP-induced metabolic reprogramming is dependent on Lin28b and that LIP enhances Lin28b expression through transcriptional repression of the let-7 microRNA family. Transgenic mice overexpressing LIP have reduced levels of let-7 in bone marrow, skin and spleen, which is associated with induction of Lin28b and hyperplasia. This study establishes LIP as a regulator of the let-7/Lin28b regulatory circuitry and we hypothesize that the LIP-controlled let-7/Lin28b regulation is involved in the de-regulation of tissue homeostasis and tumourigenesis.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-12_11:38:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guido Mastrobuoni
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2018-06-11 08:42:12	ID requested
⏵ 1	2019-11-12 11:38:40	announced

Ackermann T, Hartleben G, M, ü, ller C, Mastrobuoni G, Groth M, Sterken BA, Zaini MA, Youssef SA, Zuidhof HR, Krauss SR, Kortman G, de Haan G, de Bruin A, Wang ZQ, Platzer M, Kempa S, Calkhoven CF, /LIN28B circuit in mice. Commun Biol, 2():208(2019) [pubmed]

curator keyword: Biological

submitter keyword: shotgun proteomics, Q Exactive HF

Stefan Kempa
contact affiliation	Quantitative Proteomics and Metabolomics Berlin Institute for Medical System Biology @ Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association
contact email	stefan.kempa@mdc-berlin.de
lab head
Guido Mastrobuoni
contact affiliation	Berlin Institute for Medical Systems Biology at the Max Delbrueck Centrum for Molecular Medicine
contact email	guido.mastrobuoni@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010095
     1. Label: PRIDE project
     2. Name: C/EBPβ-LIP regulates the let-7/Lin28b circuit to induce cancer-type metabolic reprogramming