PXD019992

PXD019992 is an original dataset announced via ProteomeXchange.

Title	A miR-494 dependent feedback loop regulates ER stress (ANAN-376 Project)
Description	Defects in stress responses are important contributors in many chronic conditions including cancer, cardiovascular disease, diabetes, and obesity-driven pathologies like non-alcoholic steatohepatitis (NASH). Specifically, endoplasmic reticulum (ER) stress is linked with these pathologies and control of ER stress can ameliorate tissue damage. MicroRNAs have a critical role in regulating diverse stress responses including ER stress. Here we show that miR-494-3p plays a functional role during ER stress. ER stress inducers (tunicamycin and thapsigargin) robustly increase the expression of miR-494 in vitro in an ATF6 dependent manner. Surprisingly, miR-494 pretreatment dampens the induction and magnitude of ER stress in response to tunicamycin in endothelial cells. Conversely, inhibition of miR-494 increases ER stress de novo and amplifies the effects of ER stress inducers. Using Mass Spectrometry (TMT-MS) we identified many proteins that are downregulated by both tunicamycin and miR-494 in cultured human umbilical vein endothelial cells (HUVECs). Among these, we found 6 transcripts which harbor a putative miR-494 binding site. Our data indicates that ER stress driven miR-494 may act in a feedback inhibitory loop to dampen downstream ER stress signaling. We propose that RNA-based approaches targeting miR-494 or its targets may be attractive candidates for inhibiting ER stress dependent pathologies in human disease.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_00:32:00.466.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Phillip Wilmarth
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-24 06:59:41	ID requested
⏵ 1	2021-09-09 00:32:01	announced

Chatterjee N, Fraile-Bethencourt E, Baris A, Espinosa-Diez C, Anand S, MicroRNA-494 Regulates Endoplasmic Reticulum Stress in Endothelial Cells. Front Cell Dev Biol, 9():671461(2021) [pubmed]

submitter keyword: Endoplasmic reticulum, stress response, microRNAs, isobaric labeling, quantitative proteomics

Dr. Sudarshan Anand
contact affiliation	Department of Radiation Medicine Knight Cancer Institute and OHSU 2720 S Moody Avenue Portland, Oregon 97201, USA
contact email	anands@ohsu.edu
lab head
Phillip Wilmarth
contact affiliation	OHSU
contact email	wilmarth@ohsu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019992
     1. Label: PRIDE project
     2. Name: A miR-494 dependent feedback loop regulates ER stress (ANAN-376 Project)