MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-κB/IκBα negative feedback loop

Jiang, Lili; Lin, Chuyong; Song, Libing; Wu, Jueheng; Chen, Baixue; Ying, Zhe; Fang, Lishan; Yan, Xiao; He, Mian; Li, Jun; Li, Mengfeng

doi:10.1172/jci58849

Cited by 138 publications

(134 citation statements)

References 53 publications

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“…Transfection efficiency was measured using FITC-labeled NC by flow cytometery for every experiment. Stable cell lines expressing miR-486 and miR-486 sponge were generated via retroviral infection using HEK293T cells, as has been previously described [50], and selected by treatment with 0.5 µg/ml puromycin beginning 48 h after infection for 10 days.…”

Section: Plasmids Virus Production and Infection Of Target Cellsmentioning

confidence: 99%

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miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

Song

Lin²,

Gong³

et al. 2012

Cell Res

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Deubiquitinases, such as CYLD, A20 and Cezanne, have emerged as important negative regulators that balance the strength and the duration of NF-κB signaling through feedback mechanisms. However, how these serial feedback loops are simultaneously disrupted in cancers, which commonly exhibit constitutively activated NF-κB, remains puzzling. Herein, we report that miR-486 directly suppresses NF-κB-negative regulators, CYLD and Cezanne, as well as multiple A20 activity regulators, including ITCH, TNIP-1, TNIP-2 and TNIP-3, resulting in promotion of ubiquitin conjugations in NF-κB signaling and sustained NF-κB activity. Furthermore, we demonstrate that upregulation of miR-486 promotes glioma aggressiveness both in vitro and in vivo through activation of NF-κB signaling pathway. Importantly, miR-486 levels in primary gliomas significantly correlate with NF-κB activation status. These findings uncover a novel mechanism for constitutive NF-κB activation in gliomas and support a functionally and clinically relevant epigenetic mechanism in cancer progression.

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Section: Plasmids Virus Production and Infection Of Target Cellsmentioning

confidence: 99%

“…The procedure was carried out similarly to previously described methods [50]. The degree of immunostaining of formalin-fixed, paraffinembedded sections was reviewed and scored independently by two observers, based on both the proportion of positively stained tumor cells and the intensity of staining.…”

Section: Immunohistochemistrymentioning

confidence: 99%

miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

Song

Lin²,

Gong³

et al. 2012

Cell Res

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“…Notably, TGF-β treatment did not induce miR-182 in NHAs. Therefore, understanding the precise regulastitutively activated NF-κB signaling (42). In this study, we demonstrated a distinct mechanism by which miR-182 enhances the strength, and prolongs the duration, of NF-κB signaling through inhibition of the deubiquitination-mediated negative feedback loop.…”

Section: Figure 10mentioning

confidence: 68%

TGF-β induces miR-182 to sustain NF-κB activation in glioma subsets

Song

Liu²,

Wu³

et al. 2012

J. Clin. Invest.

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The strength and duration of NF-κB signaling are tightly controlled by multiple negative feedback mechanisms. However, in cancer cells, these feedback loops are overridden through unclear mechanisms to sustain oncogenic activation of NF-κB signaling. Previously, we demonstrated that overexpression of miR-30e* directly represses IκBα expression and leads to hyperactivation of NF-κB. Here, we report that miR-182 was overexpressed in a different set of gliomas with relatively lower miR-30e* expression and that miR-182 directly suppressed cylindromatosis (CYLD), an NF-κB negative regulator. This suppression of CYLD promoted ubiquitin conjugation of NF-κB signaling pathway components and induction of an aggressive phenotype of glioma cells both in vitro and in vivo. Furthermore, we found that TGF-β induced miR-182 expression, leading to prolonged NF-κB activation. Importantly, the results of these experiments were consistent with an identified significant correlation between miR-182 levels with TGF-β hyperactivation and activated NF-κB in a cohort of human glioma specimens. These findings uncover a plausible mechanism for sustained NF-κB activation in malignant gliomas and may suggest a new target for clinical intervention in human cancer.

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“…Tumor suppressor miRNAs are frequently down-regulated in gliomas as compared to normal brain [64][65][66][67]. In contrast, some miRNAs are defined as oncogenes with enhanced expression in glioma such as miR-21, targeting regulators, miR-10b and miR-221, targeting cell cycle inhibitors, miR-30e, and targeting IjBa [68][69][70][71]. It has been suggested that there is a link between miRNAs and well-known stem cell-regulating proteins [72].…”

Section: Epigenetics In Human Gliomas With Some Detailsmentioning

confidence: 99%

Critical Molecular and Genetic Markers in Primary Brain Tumors with Their Clinical Importance

Yaylım¹,

Azam²,

Farooqı³

et al. 2016

Neurooncology - Newer Developments

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Classification of primary brain tumors is based mainly on histopathological characteristics. Due to the peculiarity of the central nervous system (CNS), the location of the tumor is also used in the naming of the CNS tumors. These features, histopathology, and location determine the main prognostic factors in these tumors. Updated molecular and genetic findings in the last two decades accumulated vast amount of knowledge about the biological behavior, response to the treatment, and consequently the prognosis of CNS tumors. After the clinical use of these data, a recent classification is proposed by the International Society of Neuropathology named as "integrated diagnosis."This classification considers the histopathological classification, World Health Organization (WHO) grade along with the molecular information. The emerging molecular-genetic data about the CNS tumors will allow the translational researchers to deliberately understand the oncogenic mechanisms involved in the evolution of these tumors and judge the optional treatment strategies.Evaluating the check points of cell cycle and apoptosis provides valuable information about the tumor biology (tumorigenesis). These mechanisms (pathways) also play an exclusive role in CNS tumors. Knowledge concerning the gene repressors and gene activators or some epigenetic changes in proliferative and antiproliferative pathways that regarded gliomas may yield new individualized treatment options.In this chapter, we will review the basic and translational research molecular-genetic data of gliomas with special interest on proliferative and antiproliferative pathways. Further emerging treatment options and treatment responses in gliomas will be © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.critically evaluated with regard to their histopathology, anatomical location, and molecular-genetic fingerprints.

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MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-κB/IκBα negative feedback loop

Cited by 138 publications

References 53 publications

miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

miR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops

TGF-β induces miR-182 to sustain NF-κB activation in glioma subsets

Critical Molecular and Genetic Markers in Primary Brain Tumors with Their Clinical Importance

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