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Regulation of the unfolded protein response by microRNAs

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.

Abbreviations

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

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Correspondence to Rafal Bartoszewski.

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Bartoszewska, S., Kochan, K., Madanecki, P. et al. Regulation of the unfolded protein response by microRNAs. Cell Mol Biol Lett 18, 555–578 (2013). https://doi.org/10.2478/s11658-013-0106-z

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Key words

  • MicroRNA
  • Unfolded protein response
  • Adaptive response
  • Endoplasmic reticulum stress