IRE1‐mediated miRNA maturation in macrophage phosphoinositide signaling

Avril, Tony; Chevet, Éric

doi:10.15252/embr.202051929

Cited by 11 publications

(7 citation statements)

References 11 publications

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“…However, further research is necessary to clarify the role of IRE1α and its relationship to enhanced drug efflux in HCC. One important aspect of IRE1α’s endoribonuclease activity is that this is not only responsible for cleaving XBP1, but several studies have shown that IRE1α is also able to cleave and regulate miRNAs [ 45 , 46 , 47 ]. ER stress has therefore been shown to contribute to the miRNA imbalance in inflammation [ 47 ] and cancer [ 48 ].…”

Section: Mechanisms Of Drug Resistancementioning

confidence: 99%

Drug Resistance and Endoplasmic Reticulum Stress in Hepatocellular Carcinoma

Khaled

Kopsida

Lennernäs

et al. 2022

Cells

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Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide. It is usually diagnosed in an advanced stage and is characterized by a high intrinsic drug resistance, leading to limited chemotherapeutic efficacy and relapse after treatment. There is therefore a vast need for understanding underlying mechanisms that contribute to drug resistance and for developing therapeutic strategies that would overcome this. The rapid proliferation of tumor cells, in combination with a highly inflammatory microenvironment, causes a chronic increase of protein synthesis in different hepatic cell populations. This leads to an intensified demand of protein folding, which inevitably causes an accumulation of misfolded or unfolded proteins in the lumen of the endoplasmic reticulum (ER). This process is called ER stress and triggers the unfolded protein response (UPR) in order to restore protein synthesis or—in the case of severe or prolonged ER stress—to induce cell death. Interestingly, the three different arms of the ER stress signaling pathways have been shown to drive chemoresistance in several tumors and could therefore form a promising therapeutic target. This review provides an overview of how ER stress and activation of the UPR contributes to drug resistance in HCC.

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Section: Mechanisms Of Drug Resistancementioning

confidence: 99%

Drug Resistance and Endoplasmic Reticulum Stress in Hepatocellular Carcinoma

Khaled

Kopsida

Lennernäs

et al. 2022

Cells

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“…Nevertheless, several studies have identified RIDD-degraded mRNAs that encode cytosolic or nuclear proteins (including XBP1 ), illustrating that the IRE1 substrates do not necessarily require an ER a signal sequence (Kraut-Cohen and Gerst 2010 ; Pyhtila et al 2008 ; Lerner et al 2003 ; Diehn et al 2000 ). Importantly, IRE1 has also been shown to degrade several pre-miRNAs (Upton et al 2012 ; Gebert et al 2023 ) and to facilitate maturation of miRNA precursors in a DICER-independent manner (Avril and Chevet 2020 ). Because IRE1 is also localized in the inner nuclear envelope (Schroder and Kaufman 2005 ), these precursors could be processed as they encounter IRE1 while traversing the nuclear pore on their way to the cytoplasm (Upton et al 2012 ).…”

Section: The Role Of Ire1 In Cell Fate Decisionsmentioning

confidence: 99%

Dual RNase activity of IRE1 as a target for anticancer therapies

Bartoszewska,

Sławski,

Collawn

et al. 2023

J. Cell Commun. Signal.

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The unfolded protein response (UPR) is a cellular mechanism that protects cells during stress conditions in which there is an accumulation of misfolded proteins in the endoplasmic reticulum (ER). UPR activates three signaling pathways that function to alleviate stress conditions and promote cellular homeostasis and cell survival. During unmitigated stress conditions, however, UPR activation signaling changes to promote cell death through apoptosis. Interestingly, cancer cells take advantage of this pathway to facilitate survival and avoid apoptosis even during prolonged cell stress conditions. Here, we discuss different signaling pathways associated with UPR and focus specifically on one of the ER signaling pathways activated during UPR, inositol-requiring enzyme 1α (IRE1). The rationale is that the IRE1 pathway is associated with cell fate decisions and recognized as a promising target for cancer therapeutics. Here we discuss IRE1 inhibitors and how they might prove to be an effective cancer therapeutic. Graphical abstract

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“…Several works already demonstrated the involvement of IRE1 in miRNA regulation. Indeed, IRE1 regulates the expression of miR-316 and miR-148a by regulating the transcription of miRNA-related transcription factors [ 73 ]. The work from Hamid and colleagues demonstrates that IRE1 can directly control the maturation of an miRNA in a Dicer-independent fashion [ 72 ].…”

Section: Small Ncrnasmentioning

confidence: 99%

“…IRE1 is a known ER-stress sensor and promoter of adaptive stress responses caused by the accumulation of unfolded proteins in the ER. IRE1 activity can be enhanced also by the incorporation of saturated fatty acids (SFA) or free cholesterol within the ER [ 72 , 73 ]. Indeed, although the ER plays a central role in lipid metabolism, it is poor in cholesterol and SFA.…”

Section: Non-canonical Function Of Ncrnas In Cvdmentioning

confidence: 99%

A Non-Canonical Link between Non-Coding RNAs and Cardiovascular Diseases

Natarelli¹,

Weber

2022

Biomedicines

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Cardiovascular diseases (CVDs) are among the top leading causes of mortality worldwide. Besides canonical environmental and genetic changes reported so far for CVDs, non-coding RNAs (ncRNAs) have emerged as key regulators of genetic and epigenetic mechanisms involved in CVD progression. High-throughput and sequencing data revealed that almost 80% of the total genome not only encodes for canonical ncRNAs, such as micro and long ncRNAs (miRNAs and lncRNAs), but also generates novel non-canonical sub-classes of ncRNAs, such as isomiRs and miRNA- and lncRNA-like RNAs. Moreover, recent studies reveal that canonical ncRNA sequences can influence the onset and evolution of CVD through novel “non-canonical” mechanisms. However, a debate exists over the real existence of these non-canonical ncRNAs and their concrete biochemical functions, with most of the dark genome being considered as “junk RNA”. In this review, we report on the ncRNAs with a scientifically validated canonical and non-canonical biogenesis. Moreover, we report on canonical ncRNAs that play a role in CVD through non-canonical mechanisms of action.

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IRE1‐mediated miRNA maturation in macrophage phosphoinositide signaling

Cited by 11 publications

References 11 publications

Drug Resistance and Endoplasmic Reticulum Stress in Hepatocellular Carcinoma

Drug Resistance and Endoplasmic Reticulum Stress in Hepatocellular Carcinoma

Dual RNase activity of IRE1 as a target for anticancer therapies

A Non-Canonical Link between Non-Coding RNAs and Cardiovascular Diseases

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