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. 2013 Oct 2;18(4):555–578. doi: 10.2478/s11658-013-0106-z

Regulation of the unfolded protein response by microRNAs

Sylwia Bartoszewska 1, Kinga Kochan 2, Piotr Madanecki 2, Arkadiusz Piotrowski 2, Renata Ochocka 2, James F Collawn 3, Rafal Bartoszewski 2,4,✉
PMCID: PMC3877167  NIHMSID: NIHMS538574  PMID: 24092331

Abstract

The unfolded protein response (UPR) is an adaptive response to the stress that is caused by an accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER). It is an important component of cellular homeostasis. During ER stress, the UPR increases the protein-folding capacity of the endoplasmic reticulum to relieve the stress. Failure to recover leads to apoptosis. Specific cellular mechanisms are required for the cellular recovery phase after UPR activation. Using bioinformatics tools, we identified a number of microRNAs that are predicted to decrease the mRNA expression levels for a number of critical components of the UPR. In this review, we discuss the potential role of microRNAs as key regulators of this pathway and describe how microRNAs may play an essential role in turning off the UPR after the stress has subsided.

Key words: MicroRNA, Unfolded protein response, Adaptive response, Endoplasmic reticulum stress

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Abbreviations used

3′-UTR

3′-untranslated region

5′-UTR

5′-untranslated region

AD

Alzheimer’s disease

AP-1

activator protein 1

ATF4

activating transcription factor 4

ATF6

activating transcription factor 6

BAK

Bcl-2-antagonist/killer

BAX

Bcl-2-associated X protein

Bcl-2

B-cell lymphoma 2

BiP

binding immunogloblulin protein

C-2

caspase-2

C-4

caspase-4

C42B

human prostate cancer cells

Calu-3

human lung adenocarcinoma

CDK4

cyclin-dependent-kinase 4

CFTR

cystic fibrosis transmembrane conductance regulator

CHOP

C/EBP homologous protein

eIF-2α

eukaryotic initiation factor 2 alpha

ER

endoplasmic reticulum

ERAD

endoplasmic reticulum-associated degradation

ERGIC3

endoplasmic reticulum-Golgi intermediate compartment protein 3

ERp29

ER stress protein 29

GADD153

growth arrest and DNA-damage-inducible protein

GPC3

glypican-3

GRP78

glucose-regulated protein, 78 kDa

H9c2

rat heart myoblasts

HCAEC

human coronary artery endothelial cells

HCC

human hepatocellular carcinoma

HEK293T

human embryonic kidney 293T cells

HeLa

human cervical cancer cells

HTM

human trabecular meshwork cells

HUVEC

human umbilical vein endothelial cells

IRE1

inositol-requiring enzyme 1

JNK

c-JunNH2-terminal kinase

MCF-7

human breast cancer cells

MEF

mouse embryonic fibroblasts

MHC

major histocompatibility complex

NF-κB

nuclear factor kappa-lightchain-enhancer of activated B cells

NIH 3T3

mouse embryonic fibroblasts of the NIH 3T3 cell line

NRVMC

neonatal rat ventricular myocytes

PC12

pheochromocytoma 12

PERK

protein kinase RNA-like ER kinase

PSMD10

26S proteasome non-ATPase regulatory subunit 10

PUMA

p53-upregulated modulator of apoptosis

TAP1

transporter associated with antigen processing 1

TF

transcription factor

TXNIP

thioredoxininteracting protein

UPR

unfolded protein response

VEGF

vascular endothelial growth factor

XBP1

X-box binding protein 1

XBP1(s)

spliced XBP1

Footnotes

These authors contributed equally to this work.

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