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Regulation of the unfolded protein response by microRNAs


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.



3′-untranslated region


5′-untranslated region


Alzheimer’s disease


activator protein 1


activating transcription factor 4


activating transcription factor 6




Bcl-2-associated X protein


B-cell lymphoma 2


binding immunogloblulin protein






human prostate cancer cells


human lung adenocarcinoma


cyclin-dependent-kinase 4


cystic fibrosis transmembrane conductance regulator


C/EBP homologous protein


eukaryotic initiation factor 2 alpha


endoplasmic reticulum


endoplasmic reticulum-associated degradation


endoplasmic reticulum-Golgi intermediate compartment protein 3


ER stress protein 29


growth arrest and DNA-damage-inducible protein




glucose-regulated protein, 78 kDa


rat heart myoblasts


human coronary artery endothelial cells


human hepatocellular carcinoma


human embryonic kidney 293T cells


human cervical cancer cells


human trabecular meshwork cells


human umbilical vein endothelial cells


inositol-requiring enzyme 1


c-JunNH2-terminal kinase


human breast cancer cells


mouse embryonic fibroblasts


major histocompatibility complex


nuclear factor kappa-lightchain-enhancer of activated B cells

NIH 3T3:

mouse embryonic fibroblasts of the NIH 3T3 cell line


neonatal rat ventricular myocytes


pheochromocytoma 12


protein kinase RNA-like ER kinase


26S proteasome non-ATPase regulatory subunit 10


p53-upregulated modulator of apoptosis


transporter associated with antigen processing 1


transcription factor


thioredoxininteracting protein


unfolded protein response


vascular endothelial growth factor


X-box binding protein 1


spliced XBP1


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Correspondence to Rafal Bartoszewski.

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These authors contributed equally to this work.

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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).

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Key words

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