Merlin negative regulation by miR-146a promotes cell transformation

Pérez-García, Erick I.; Meza-Sosa, Karla F.; López-Sevilla, Yaxem; Camacho-Concha, Nohemí; Sánchez, Nilda; Pérez-Martı́nez, Leonor; Pedraza‐Alva, Gustavo

doi:10.1016/j.bbrc.2015.10.156

Cited by 9 publications

(16 citation statements)

References 22 publications

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“…We also recently showed that Merlin levels are negatively regulated by different microRNAs (miRNAs). We found that miR-146a, miR-7, miR-25, and miR-32 reduces Merlin protein levels and that miR-146a and miR-7 enhances malignant transformation of lung cells (Perez-Garcia et al, 2015).…”

Section: Introductionmentioning

confidence: 72%

“…Luciferase assays were performed with psiCHECK empty vector (Promega) as a control, and the NF2-3¢UTR fragment (Luc-wtNF2-3¢UTR) or a mutant version of the NF2-3¢UTR (Luc-mutNF2-3¢UTR) was cloned downstream from luciferase in the psiCHECK vector. These plasmids have been previously described (Perez-Garcia et al, 2015).…”

Section: Plasmid Constructsmentioning

confidence: 99%

“…Stable cell lines generated from A549 cells (those transfected with pcDNA, miR-146a, and miR-146a/NF2) were previously established (Perez-Garcia et al, 2015). Clones with different miR-146a expression levels (High, Low1, Low2, and Low3) were obtained by limiting dilution of A549 cells in a 96-well plate.…”

Section: Stable Cell Lines and Generation Of Clonesmentioning

confidence: 99%

“…We have recently shown that miR-146a potentiates the migratory and invasive abilities of the lung tumor cell line A549 through a mechanism that partly involves the negative regulation of the tumor suppressor, Merlin (Perez-Garcia et al, 2015). We considered the following: (i) proinflammatory cytokines such as TNF and IL-1b also promote a metastatic phenotype in A549 cells (Kawata et al, 2012), (ii) miR-146a expression is regulated by these cytokines (Kutty et al, 2013), and (iii) miR-7, miR-32 and miR-330 which negatively regulate Merlin (Perez-Garcia et al, 2015), are associated with tumor progression (Mesci et al, 2017;Shen et al, 2017;Xia et al, 2017). Therefore, we evaluated whether TNF regulates the expression of these miRNAs in A549 cells.…”

Section: Tnf Promotes the Expression Of Mirnas That Target Merlinmentioning

confidence: 99%

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Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin

Sánchez

Medrano-Jiménez

Aguilar‐León

et al. 2020

DNA and Cell Biology

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Inflammation plays a key role in carcinogenesis and metastasis. This process involves the inactivation of tumor suppressor molecules, yet the molecular mechanisms by which inflammation impairs tumor suppressors are not completely understood. In this study, we show that proinflammatory signals such as tumor necrosis factor (TNF) support lung cancer metastasis by reducing the levels of the tumor suppressor Merlin through regulation of miR-146a. Immunodeficient mice inoculated with A549 cells expressing high miR-146a levels and low Merlin protein levels exhibited reduced survival, which correlated with the number of metastatic nodes formed. Accordingly, restoring Merlin protein levels inhibited metastasis and increased survival of the mice. Consistent with these results, we found that elevated miR-146a expression levels correlated with low Merlin protein levels in human lung adenocarcinoma. Furthermore, human invasive and metastatic tumors showed higher TNF and miR-146a levels, but lower Merlin protein levels than noninvasive tumors. These findings indicate that upregulation of miR-146a by TNF in lung adenocarcinoma promotes Merlin protein inhibition and metastasis. Thus, we suggest that the ratio between miR-146a and Merlin protein levels could be a relevant molecular biomarker that can predict lung cancer progression and that the TNF/miR-146a/Merlin pathway is a promising new therapeutic target to inhibit lung adenocarcinoma progression.

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Section: Introductionmentioning

confidence: 72%

Section: Plasmid Constructsmentioning

confidence: 99%

Section: Stable Cell Lines and Generation Of Clonesmentioning

confidence: 99%

Section: Tnf Promotes the Expression Of Mirnas That Target Merlinmentioning

confidence: 99%

See 2 more Smart Citations

Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin

Sánchez

Medrano-Jiménez

Aguilar‐León

et al. 2020

DNA and Cell Biology

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“…Through imperfect pairing with the 3′-untranslated regions (3′-UTRs) of mRNA, they can regulate target gene expression at the post-transcriptional level by inhibiting translation or by increasing messenger RNA (mRNA) degradation [6]. Recent evidence indicates that miRNA levels are closely correlated with tumor metastasis and proliferation [7]. For example, miR-145 and miR-218 suppress GC cell metastasis by inhibiting the expression of N-cadherin and Robo1, respectively [8].…”

Section: Introductionmentioning

confidence: 99%

MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B

et al. 2016

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MicroRNAs are critical in various human cancers, including gastric cancer (GC). However, the mechanism underlying the GC development remains elusive. In this study, we demonstrate that miR-448 is increased in GC samples and cell lines. Overexpression of miR-448 facilitated the proliferation of GC cells by stimulating glycolysis. Mechanistically, we identified KDM2B, a reader for methylated CpGs, as the target of miR-448 that represses glycolysis and promotes oxidative phosphorylation. Overexpression of miR-448 reduced both the mRNA and protein levels of KDM2B, whereas KDM2B re-expression abrogated the miR-448-mediated glycolytic activities. Furthermore, we discovered Myc as a key target of KDM2B that controls metabolic switch in GC. Importantly, a cohort of 81 GC tissues revealed that miR-448 level closely associated with a battery of glycolytic genes, in which KDM2B showed the strongest anti-correlation coefficient. In addition, enhanced miR-448 level was significantly associated with poor clinical outcomes of GC patients. Hence, we identified a previously unappreciated mechanism by which miR-448 orchestrate epigenetic, transcriptional and metabolic networks to promote GC progression, suggesting the possibility of therapeutic intervention against cancer metabolic pathways.

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WITHDRAWN: Exposure to an enriched environment improves colonic epithelial barrier integrity and attenuates mouse experimental colitis by modulating a Myc-driven gene regulatory network

Villa-Señor-Toledo

Valle-García

Pop

et al. 2023

Preprint

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Cumulative evidence suggests that somatosensorial stimulation through exposure to enriched environments improves homeostasis and enhances central nervous system functions. Immune system functions are also modulated by exposure to enriched environments, which enhance phagocytosis and chemotaxis while attenuating the inflammatory response induced by lipopolysaccharide exposure or hypercaloric diets. Consistent with these, here we show that exposure to an enriched environment attenuates inflammation in the colon in two colitis experimental models. Exposing animals to an enriched environment reduced weight loss, colon length shortening, and decreased disease activity index after dextran sodium sulfate or trinitrobenzene sulfonic acid treatment, compared with animals housed in a normal environment. Histologically, after colitis induction, exposure to an enriched environment reduced epithelial damage, lessened the inflammation, and attenuated loss of goblet cells compared to animals housed in a normal environment. Our results also show that brain stimulation by exposure to an enriched environment attenuates inflammation in the intestinal mucosa by preventing epithelial barrier dysfunction through BDNF-mediated expression of cell adhesion molecules. At the molecular level, there is a global change in gene expression and gene regulatory networks as a response to dextran treatment. Interestingly, a Myc-driven gene regulatory network enhanced by colitis is attenuated by exposure to an enriched environment, via downmodulation of Myc protein levels. Together, our results show that brain stimulation by exposure to an enriched environment attenuates inflammation in the gut mucosa by fine-tuning an inflammatory gene expression program, opening new venues of investigation for colitis treatment.

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Merlin negative regulation by miR-146a promotes cell transformation

Cited by 9 publications

References 22 publications

Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin

Tumor Necrosis Factor-Induced miR-146a Upregulation Promotes Human Lung Adenocarcinoma Metastasis by Targeting Merlin

MiR-448 promotes glycolytic metabolism of gastric cancer by downregulating KDM2B

WITHDRAWN: Exposure to an enriched environment improves colonic epithelial barrier integrity and attenuates mouse experimental colitis by modulating a Myc-driven gene regulatory network

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