PXD073651

PXD073651 is an original dataset announced via ProteomeXchange.

Title	Computationally guided prioritization of microRNA therapeutics for metabolic dysfunction-associated steatohepatitis: inhibition of hepatic stellate cell activation
Description	Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease characterized by chronic inflammation and fibrosis, for which effective therapies remain limited. Given the multifactorial nature of MASH, therapeutic approaches capable of modulating complex regulatory networks are required. To identify fibrosis-relevant targets and therapeutic microRNAs (miRNAs), we established an integrative workflow combining cellular models, quantitative proteomics and bioinformatic analyses. Proteomic profiling was performed in LX-2 cells, an immortalized human hepatic stellate cell (HSC) line, activated with transforming growth factor β1 (TGF-β1) to model a profibrotic phenotype. Proteins upregulated upon activation were analyzed using two complementary miRNA target prediction strategies: experimentally validated miRNA–target interactions curated in miRTarBase and computational predictions generated using the miRNA binding sites (MBS) tool. Among the identified candidates, the collagen-modifying enzyme prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was selected for proof-of-concept validation. Functional screening of five miRNA mimics predicted to target P4HA2 identified miR-9-5p as the most effective candidate, capable of reducing P4HA2 protein levels and suppressing key profibrotic markers. Antifibrotic activity was further validated in HepG2/LX-2 co-culture liver spheroids, where collagen modulation was confined to the HSC-like cell compartment. Together, these data identify P4HA2 as a functionally relevant therapeutic target in activated HSCs and demonstrate the value of computationally guided miRNA prioritization for antifibrotic therapy development in MASH.
HostingRepository	PRIDE
AnnounceDate	2026-09-02
AnnouncementXML	Submission_2026-09-02_06:46:10.230.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Margot Lo Pinto
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-27 10:25:32	ID requested
⏵ 1	2026-09-02 06:46:11	announced

Dataset with its publication pending

submitter keyword: type I collagen-α1, LX-2 cells, HepG2 cells, fibrosis,MASH, miRNA mimics

Simone Dario Scilabra
contact affiliation	Fondazione Ri.Med Department of Laboratory Medicine and Advanced Biotechnologies, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS - ISMETT) Via Ernesto Tricomi, 5 - 90127 Palermo
contact email	sdscilabra@fondazionerimed.com
lab head
Margot Lo Pinto
contact affiliation	Fondazione Ri.MED
contact email	mlopinto@fondazionerimed.com
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/2026/09/PXD073651

PRIDE project URI

• PRIDE
  1. PXD073651
     1. Label: PRIDE project
     2. Name: Computationally guided prioritization of microRNA therapeutics for metabolic dysfunction-associated steatohepatitis: inhibition of hepatic stellate cell activation