miR-211 Is a Prosurvival MicroRNA that Regulates chop Expression in a PERK-Dependent Manner

Chitnis, Nilesh; Pytel, Dariusz; Bobrovnikova-Marjon, Ekaterina; Pant, Dhruv K.; Zheng, Hui; Maas, Nancy L.; Frederick, Brian; Kushner, Jake A.; Chodosh, Lewis A.; Koumenis, Constantinos; Fuchs, Serge Y.; Diehl, J. Alan

doi:10.1016/j.molcel.2012.08.025

Cited by 188 publications

(159 citation statements)

References 50 publications

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“…Each one of the UPR sensors relays information on the protein folding status from the ER lumen to the nucleus, thereby controlling gene expression. 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).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

Maurel

Dejeans

Taouji

et al. 2013

RNA

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“…miR-211 was reported to reduce ER stress in colorectal cancer (18). miR-204, another member of the miR-211 family, increases the sensitivity to oxidative stress in neuron cells (47).…”

Section: Association Between Fam213a Expression and Poor Patient Survmentioning

confidence: 99%

“…A recent study has also specified that miR-211 prevents the ER induction by transcriptional repression of C/EBP homologous protein (CHOP) to modulate the survival of cells (18). Despite that miR-211 is a tumor suppressor in melanoma and some other cancers (19)(20)(21), the function of miR-211 as an oncogenic molecule has become more evident in a fraction of malignancies (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity

Chen¹,

et al. 2016

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miR-211 expression in human oral squamous cell carcinoma (OSCC) has been implicated in poor patient survival. To investigate the oncogenic roles of miR-211, we generated K14-EGFPmiR-211 transgenic mice tagged with GFP. Induction of oral carcinogenesis in transgenic mice using 4-nitroquinoline 1-oxide (4NQO) resulted in more extensive and severe tongue tumorigenesis compared with control animals. We found that 4NQO and arecoline upregulated miR-211 expression in OSCC cells. In silico and experimental evidence further revealed that miR-211 directly targeted transcription factor 12 (TCF12), which mediated suppressor activities in OSCC cells and was drastically downregulated in tumor tissues. We used GeneChip analysis and bioinformatic algorithms to identify transcriptional targets of TCF12 and confirmed through reporter and ChIP assays that family with sequence similarity 213, member A (FAM213A), a peroxiredoxin-like antioxidative protein, was repressed transcriptionally by TCF12. FAM213A silencing in OSCC cells diminished oncogenic activity, reduced the ALDH1-positive cell population, and increased reactive oxygen species. TCF12 and FAM213A expression was correlated inversely in head and neck carcinoma samples according to The Cancer Genome Atlas. OSCC patients bearing tumors with high FAM213A expression tended to have worse survival. Furthermore, 4NQO treatment downregulated TCF12 and upregulated FAM213A by modulating miR-211 both in vitro and in vivo. Overall, our findings develop a mouse model that recapitulates the molecular and histopathologic alterations of human OSCC pathogenesis and highlight a new miRNA-mediated oncogenic mechanism. Cancer Res; 76(16); 4872-86. Ó2016 AACR.

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“…To date, functional studies on a few miRNAs have been conducted in primary cell cultures, revealing their roles in the regulation of angiogenesis of the choriocapillaris, in prevention of oxidative damage, and in maintaining barrier functions and epithelial physiology of cultured RPE (Haque et al, 2012;Lin et al, 2011;Wang et al, 2010). Moreover, miRNAs are associated with endoplasmic reticulum stress, which is a hallmark of AMD and results in altered expression of tight-junction molecules and apoptosis genes (Byrd et al, 2012;Chitnis et al, 2012;Yoshikawa et al, 2011). These findings led to the hypothesis that miRNAs are involved in processes that are crucial for the normal physiology of the RPE and of the adjacent tissues, namely the choroid and retina.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs of the RPE are essential for RPE differentiation and photoreceptor maturation

et al. 2015

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Dysfunction of the retinal pigmented epithelium (RPE) results in degeneration of photoreceptors and vision loss and is correlated with common blinding disorders in humans. Although many proteincoding genes are known to be expressed in RPE and are important for its development and maintenance, virtually nothing is known about the in vivo roles of non-coding transcripts. The expression patterns of microRNAs (miRNAs) have been analyzed in a variety of ocular tissues, and a few were implicated to play role in RPE based on studies in cell lines. Here, through RPE-specific conditional mutagenesis of Dicer1 or Dgcr8 in mice, the importance of miRNAs for RPE differentiation was uncovered. miRNAs were found to be dispensable for maintaining RPE fate and survival, and yet they are essential for the acquisition of important RPE properties such as the expression of genes involved in the visual cycle pathway, pigmentation and cell adhesion. Importantly, miRNAs of the RPE are required for maturation of adjacent photoreceptors, specifically for the morphogenesis of the outer segments. The alterations in the miRNA and mRNA profiles in the Dicer1-deficient RPE point to a key role of miR-204 in regulation of the RPE differentiation program in vivo and uncover the importance of additional novel RPE miRNAs. This study reveals the combined regulatory activity of miRNAs that is required for RPE differentiation and for the development of the adjacent neuroretina.

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miR-211 Is a Prosurvival MicroRNA that Regulates chop Expression in a PERK-Dependent Manner

Cited by 188 publications

References 50 publications

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

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

MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity

MicroRNAs of the RPE are essential for RPE differentiation and photoreceptor maturation

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