The Yin and Yang of hsa-miR-1244 expression levels during activation of the UPR control cell fate

Paulina Czechowicz; Magdalena Gebert; Sylwia Bartoszewska; Leszek Kalinowski; James F. Collawn; Rafał Bartoszewski

doi:10.1186/s12964-024-01967-2

The Yin and Yang of hsa-miR-1244 expression levels during activation of the UPR control cell fate

Abstract

Regulation of endoplasmic reticulum (ER) homeostasis plays a critical role in maintaining cell survival. When ER stress occurs, a network of three pathways called the unfolded protein response (UPR) is activated to reestablish homeostasis. While it is known that there is cross-talk between these pathways, how this complex network is regulated is not entirely clear. Using human cancer and non-cancer cell lines, two different genome-wide approaches, and two different ER stress models, we searched for miRNAs that were decreased during the UPR and surprisingly found only one, miR-1244, that was found under all these conditions. We also verified that ER-stress related downregulation of miR-1244 expression occurred with 5 different ER stressors and was confirmed in another human cell line (HeLa S3). These analyses demonstrated that the outcome of this reduction during ER stress supported both IRE1 signaling and elevated BIP expression. Further analysis using inhibitors specific for IRE1, ATF6, and PERK also revealed that this miRNA is impacted by all three pathways of the UPR. This is the first example of a complex mechanism by which this miRNA serves as a regulatory check point for all 3 pathways that is switched off during UPR activation. In summary, the results indicate that ER stress reduction of miR-1244 expression contributes to the pro-survival arm of UPR.

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Authors (6)

Paulina Czechowicz
Magdalena Gebert
Sylwia Bartoszewska
Leszek Kalinowski prof. dr hab. lek.
James F. Collawn
Rafał Bartoszewski

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DOI:: Digital Object Identifier (open in new tab) 10.1186/s12964-024-01967-2
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Keywords

UPR, ER STRESS, MIRNA, MICRORNA, CELL FATE DECISIONS

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Category:

Articles

Type:

artykuły w czasopismach

Published in:

Cell Communication and Signaling no. 22,
ISSN: 1478-811X

Language:

English

Publication year:

2024

Bibliographic description:

Czechowicz P., Gebert M., Bartoszewska S., Kalinowski L., Collawn J. F., Bartoszewski R.: The Yin and Yang of hsa-miR-1244 expression levels during activation of the UPR control cell fate// Cell Communication and Signaling -Vol. 22,iss. 1 (2024),

DOI:

10.1186/s12964-024-01967-2

Sources of funding:

This work has been supported by National Science Center “OPUS” Program under contract UMO-2020/37/B/NZ3/00861 (to R.B). L.K. was funded by the Polish Ministry of Science and Higher Education award no 2/566516/SPUB/SP/2023.

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