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

Libing Song, Chuyong Lin, Hui Gong, Chanjuan Wang, Liping Liu, Jueheng Wu, Sha Tao, Bo Hu, Shi-Yuan Cheng, Mengfeng Li, Jun Li*

*Corresponding author for this work

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)274-289
Number of pages16
JournalCell Research
Volume23
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Glioma
Ubiquitin
Epigenomics
Neoplasms
Up-Regulation
Deubiquitinating Enzymes
In Vitro Techniques

Keywords

  • NF-κB
  • aggressiveness
  • gliomas
  • miR-486
  • ubiquitin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Song, L., Lin, C., Gong, H., Wang, C., Liu, L., Wu, J., ... Li, J. (2013). MiR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops. Cell Research, 23(2), 274-289. https://doi.org/10.1038/cr.2012.174
Song, Libing ; Lin, Chuyong ; Gong, Hui ; Wang, Chanjuan ; Liu, Liping ; Wu, Jueheng ; Tao, Sha ; Hu, Bo ; Cheng, Shi-Yuan ; Li, Mengfeng ; Li, Jun. / MiR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops. In: Cell Research. 2013 ; Vol. 23, No. 2. pp. 274-289.
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Song, L, Lin, C, Gong, H, Wang, C, Liu, L, Wu, J, Tao, S, Hu, B, Cheng, S-Y, Li, M & Li, J 2013, 'MiR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops', Cell Research, vol. 23, no. 2, pp. 274-289. https://doi.org/10.1038/cr.2012.174

MiR-486 sustains NF-κB activity by disrupting multiple NF-κB-negative feedback loops. / Song, Libing; Lin, Chuyong; Gong, Hui; Wang, Chanjuan; Liu, Liping; Wu, Jueheng; Tao, Sha; Hu, Bo; Cheng, Shi-Yuan; Li, Mengfeng; Li, Jun.

In: Cell Research, Vol. 23, No. 2, 01.02.2013, p. 274-289.

Research output: Contribution to journalArticle

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AU - Lin, Chuyong

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AU - Liu, Liping

AU - Wu, Jueheng

AU - Tao, Sha

AU - Hu, Bo

AU - Cheng, Shi-Yuan

AU - Li, Mengfeng

AU - Li, Jun

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