The Unfolded Protein Response (UPR)-activated Transcription Factor X-box-binding Protein 1 (XBP1) Induces MicroRNA-346 Expression That Targets the Human Antigen Peptide Transporter 1 (TAP1) mRNA and Governs Immune Regulatory Genes

Bartoszewski, Rafał; Brewer, Joseph W.; Rab, András; Crossman, David K.; Bartoszewska, Sylwia; Kapoor, Niren; Fuller, Catherine M.; Collawn, James F.; Bebök, Zsuzsa

doi:10.1074/jbc.m111.304956

Cited by 132 publications

(129 citation statements)

References 55 publications

(57 reference statements)

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“…The PERK branch was described to control the expression of miR-708 (Behrman et al 2011), miR-106b-25 (Gupta et al 2012), miR-30c-2 * (Byrd et al 2012), and miR-211 (Chitnis et al 2012). In the same way, ATF6 signaling down-regulates the expression of miR-455 (Belmont et al 2012), and IRE1α signaling increases that of miR-346 (Bartoszewski et al 2011). Recently, miR-122, the most abundant miRNA in the liver, whose expression is repressed in HCC, was found to inhibit CDK4, which interacts and induces accumulation of PSMD10, a proteasome component and an enhancer of the UPR (Yang et al 2011).…”

Section: Discussionmentioning

confidence: 97%

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

Maurel

Dejeans

Taouji

et al. 2013

RNA

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MicroRNAs (miRNA) are generally described as negative regulators of gene expression. However, some evidence suggests that they may also play positive roles. As such, we reported that miR-1291 leads to a GPC3 mRNA expression increase in hepatoma cells through a 3 ′ untranslated region (UTR)-dependent mechanism. In the absence of any direct interaction between miR-1291 and GPC3 mRNA, we hypothesized that miR-1291 could act by silencing a negative regulator of GPC3 mRNA expression. Based on in silico predictions and experimental validation, we demonstrate herein that miR-1291 represses the expression of the mRNA encoding the endoplasmic reticulum (ER)-resident stress sensor IRE1α by interacting with a specific site located in the 5 ′ UTR. Moreover, we show, in vitro and in cultured cells, that IRE1α cleaves GPC3 mRNA at a 3 ′ UTR consensus site independently of ER stress, thereby prompting GPC3 mRNA degradation. Finally, we show that the expression of a miR-1291-resistant form of IRE1α abrogates the positive effects of miR-1291 on GPC3 mRNA expression. Collectively, our data demonstrate that miR-1291 is a biologically relevant regulator of GPC3 expression in hepatoma cells and acts through silencing of the ER stress sensor IRE1α.

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Section: Discussionmentioning

confidence: 97%

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

Maurel

Dejeans

Taouji

et al. 2013

RNA

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“…Therefore, mRNA degradation and the role of miRNAs during the UPR should be carefully considered. Our previous studies indicated that only a small number of miRNAs were induced to express under ER stress, while the majority were either unaffected or downregulated [51]. Recent studies continue to support the idea that UPRadaptive transcription factors can be governed by miRNAs [53,54], and transcription factors can regulate miRNA expression [51] or stability [55].…”

Section: Micrornasmentioning

confidence: 99%

“…They also govern the cellular response to ER stress by controlling both adaptive and apoptotic mechanisms. Behrman et al [52] and our group [51] have shown that ER stress induced by unrelated mechanisms (blocking proteasomal degradation, blocking ER-dependent glycosylation or disturbing Ca 2+ homeostasis) affects the miRNA expression patterns in different ways. Although most of the observed differences are presumably caused by basic mechanisms underlying the type of stress induction, some may be related to the different impact of those stressors on the dynamics of the UPR adaptive response.…”

Section: Micrornasmentioning

confidence: 99%

“…However, we are just beginning to understand their impact on cellular stress responses, such as hypoxia [45,46], oxidative stress [47,48], and various types of UPR activation, including insulin secretion [49] and B-cell differentiation [50]. During the UPR, mRNA and protein levels are decreased in order to reduce ER load, but surprisingly, the transcription of only a small percentage of genes is reduced [51,52]. Therefore, mRNA degradation and the role of miRNAs during the UPR should be carefully considered.…”

Section: Micrornasmentioning

confidence: 99%

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Regulation of the unfolded protein response by microRNAs

Bartoszewska¹,

Kochan²,

Madanecki³

et al. 2013

Cellular and Molecular Biology Letters

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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.

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“…Functional studies revealed that TAP1 is a direct target of miRNA-346 using overexpression and RNAi knockdown experiments with miRNA mimic and miRNA inhibitors. The ER stress-mediated MHC class I-associated antigen presentation decrease might be explained by increased miRNA-346 expression [65], although the function of miRNA-346 in cancer has not yet been fully analyzed.…”

Section: Antigen Processing and Presentation Machinery And Mirnasmentioning

confidence: 99%

The Role of Immune Modulatory MicroRNAs in Tumors

Seliger¹,

Meinhardt²,

Falke³

2016

RNA Interference

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Tumors could evade the control of CD8 + T and/or NK cell-mediated surveillance by distinct immune escape strategies. These include the aberrant expression of HLA class I antigens, coinhibitory or costimulatory molecules, and components of the interferon (IFN) signal transduction pathway. In addition, alterations of the tumor microenvironment could interfere with a proper antitumoral immune response by downregulating or inhibiting the frequency and/or activity of immune effector cells and professional antigen presenting cells. Based on the identification as major mediators of the posttranscriptional silencing of gene expression, microRNAs (miRNAs) have been suggested to play a key role in many biological processes known to be involved in neoplastic transformation. Indeed, miRNA expression is frequently deregulated in many cancer types and could have tumor-suppressive as well as oncogenic potential. This review focused on the characterization of miRNAs, which are involved in the control of the immune surveillance or immune escape of tumors and their use as potential diagnostic and prognostic biomarkers as well as therapeutic targets. Moreover, miRNAs can have dual activities by affecting the neoplastic and immunogenic phenotype of tumors.

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The Unfolded Protein Response (UPR)-activated Transcription Factor X-box-binding Protein 1 (XBP1) Induces MicroRNA-346 Expression That Targets the Human Antigen Peptide Transporter 1 (TAP1) mRNA and Governs Immune Regulatory Genes

Cited by 132 publications

References 55 publications

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression

Regulation of the unfolded protein response by microRNAs

The Role of Immune Modulatory MicroRNAs in Tumors

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