期刊
CANCER LETTERS
卷 396, 期 -, 页码 1-9出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.03.002
关键词
Glioma; Non-coding RNA; Mesenchymal transition; Transcriptome subtype; NF-kappa B signaling
类别
资金
- National Natural Science Foundation of China [81402052]
- Beijing Nova Program [Z16110004916082]
- Beijing Postdoctoral Research Foundation [2016ZZ-37]
- National Key Research and Development Plan [2016YFC0902500]
- Beijing Science and Technology Plan [Z131100006113018, Z141100000214009]
- Capital Medical Development Research Fund [2016-1-1072]
- Research Special Fund for Public Welfare Industry of Heath [201402008]
The mesenchymal (MES) subtype of glioblastoma (GBM) indicated a more malignant phenotype and worse prognosis compared with their proneural (PN) counterpart. The plasticity between PN and MES transcriptome signatures provided an approach for clinical intervention. However, few miRNAs have been identified to participate in the shift between subtypes. Here, we utilized transcriptomic data and experimental evidences to prove that miR-181d was a novel regulator of NF kappa B signaling pathway by directly repressing MALT1, leading to induced PN markers and reduced MES genes. Functionally, ectopic expression of miR-181d suppressed GBM cell proliferation, colony formation and anchor-independent growth, as well as migration, invasion and tube formation. Moreover, miR-181d overexpression increased radio- and chemo-sensitivity for GBM cells. Rescue of MALT1 could partially reverse the effects of miR-181d in GBM malignant behaviors. Clinically, miR-181d could serve as a prognostic indicator for GBM patients. Taken together, we concluded that loss of miR-181d contributes to aggressive biological processes associated with MES phenotype via NF kappa B signaling, which broaden our insights into the underlying mechanisms in subtype transition and miRNA-based tailored medicine for GBM management. (C) 2017 Elsevier B.V. All rights reserved.
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