PXD044478-1

PXD044478 is an original dataset announced via ProteomeXchange.

Title	Combinatorial targeting of the miR-379/miR-410 cluster normalizes glucose and lipid homeostasis in diabetes and obesity
Description	Non-coding RNAs from the Dlk1-Dio3 locus are critical for the maturation of metabolic tissues in early stages of postnatal development; however, their role in the mature organs remains elusive. Herein, we show that microRNAs from the miR-379/miR-410 cluster are robustly upregulated in livers of obese human subjects and various mouse models of metabolic dysfunction. Adult-onset, combinatorial inhibition of this miRNA cluster by hepatocyte-specific expression of a decoy sequence induced profound reductions in triglyceride, total and LDL cholesterol circulating levels, as well as decreased basal glycemia and improved glucose tolerance and insulin sensitivity. Consistent with the decoy-triggered enhancement of PI3K/mTOR signaling in these mice, hepatocytes expressing the combinatorial decoy showed augmented mitochondrial mass and function. Notably, decoy therapy led to vast improvements in glucose and lipid homeostasis in both type 1 diabetic and diet-induced, type 2 pre-diabetic, obese animals with no discernable side effects. Collectively, our results demonstrate that microRNAs from the miR-379/miR-410 cluster are critical regulators of metabolic homeostasis in the mature liver. Given the preservation of miRNA dysfunction in human obesity, combinatorial inhibition of an entire miRNA cluster by decoy-mediated targeting represents an unprecedented approach towards multi-parameter improvements in diabetes and obesity.
HostingRepository	PRIDE
AnnounceDate	2026-07-30
AnnouncementXML	Submission_2026-07-30_04:28:13.830.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Juliane Merl-Pham
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-10 04:13:45	ID requested
⏵ 1	2026-07-30 04:28:14	announced

Dataset with its publication pending

submitter keyword: liver,microRNA, mouse

Stephan Herzig
contact affiliation	Institute for Diabetes and Cancer, Helmholtz Munich, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany; German Center for Diabetes Research (DZD), and German Center for Cardiovascular Disease (DZHK), Neuherberg, Germany; Chair Molecular Metabolic Control, Technical University Munich, Germany
contact email	stephan.herzig@helmholtz-munich.de
lab head
Juliane Merl-Pham
contact affiliation	Metabolomics and Proteomics Core, Helmholtz Munich
contact email	juliane.merl@helmholtz-muenchen.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/07/PXD044478

PRIDE project URI

• PRIDE
  1. PXD044478
     1. Label: PRIDE project
     2. Name: Combinatorial targeting of the miR-379/miR-410 cluster normalizes glucose and lipid homeostasis in diabetes and obesity