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Cylindromatosis (CYLD) is a tumor suppressor that regulates signaling pathways by acting as a deubiquitinase. CYLDdown-regulation occurred in several malignancies, with tumor-promoting effects. Although Guo et al. found loss of CYLD expression in hypoxic regions of human glioblastoma multiforme (GBM), biological roles of CYLD in GBM remain unknown.

CYLD overexpression strongly counteracted these responses. In addition, chronic anti-angiogenic therapy with bevacizumab, with enhanced hypoxia produced responses similar to these CYLD-regulated proinflammatory responses in a xenograft mouse model. Histologically, CYLD clearly prevented massive immune cell infiltration surrounding necrotic regions, and pseudopalisades appeared in bevacizumab-treated control tumors. Furthermore, CYLD overexpression, which had no impact on survival by itself, significantly improved the prosurvival effect of bevacizumab. These data suggest that CYLD down-regulation is crucial for hypoxia-mediated inflammation in GBM, which may affect the long-term efficacy of anti-VEGF therapy 1).

Dual-luciferase assays identified that the cylindromatosis (CYLD) gene is a direct target of miR 130b. Functional studies demonstrated that a miR-130b mimic significantly promoted the growth and invasion of glioma cells, while also inhibiting apoptosis via selective targeting of CYLD, which was enhanced by CYLD-targeted siRNA. In contrast, a miR‑130b inhibitor suppressed these biological behaviors, and this inhibition was reversed by CYLD-targeted siRNA 2).

miR 181d is required for dendritic cells (DCs) maturation through the activation of Nuclear factor kappa pathway by targeting cylindromatosis CYLD 3).

Guo J, Shinriki S, Su Y, Nakamura T, Hayashi M, Tsuda Y, Murakami Y, Tasaki M, Hide T, Takezaki T, Kuratsu J, Yamashita S, Ueda M, Li JD, Ando Y, Jono H. Hypoxia suppresses cylindromatosis (CYLD) expression to promote inflammation in glioblastoma: possible link to acquired resistance to anti-VEGF therapy. Oncotarget. 2014 Aug 15;5(15):6353-64. PubMed PMID: 25071012; PubMed Central PMCID: PMC4171635.
Xiao ZQ, Yin TK, Li YX, Zhang JH, Gu JJ. miR-130b regulates the proliferation, invasion and apoptosis of glioma cells via targeting of CYLD. Oncol Rep. 2017 Jul;38(1):167-174. doi: 10.3892/or.2017.5651. Epub 2017 May 19. PubMed PMID: 28534976.
Su XW, Lu G, Leung CK, Liu Q, Li Y, Tsang KS, Zhao SD, Chan DTM, Kung HF, Poon WS. miR-181d regulates human dendritic cell maturation through NF-κB pathway. Cell Prolif. 2017 Jul 21. doi: 10.1111/cpr.12358. [Epub ahead of print] PubMed PMID: 28731516.
cylindromatosis.txt · Last modified: 2017/07/22 17:03 by administrador