Journal
BRITISH JOURNAL OF CANCER
Volume 117, Issue 7, Pages 1036-1047Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2017.255
Keywords
gliomas; miR-29; CDC42; migration; invasion; prognostic biomarkers
Categories
Funding
- National Basic Research Program of China (973 Program) [2010CB529405]
- National Natural Science Foundation of China [81402050, 81502166, 81672592]
- Programs of Science and Technology Commission Foundation of Tianjin Municipality [15JCYBJC49900, 15JCZDJC34600, 16JCQNJC13400, 17JCYBJC27100]
- Program of Tianjin Municipal Health Bureau [15KJ147]
- Foundation of Tianjin Medical University and General Hospital [2013KYQ02, 2014KYQ02, 2015KYZQ11, ZYYFY2014038, ZYYFY2015032]
- 'Junior Technical Gackbone' Training Project of TMUGH
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Background: The lethality and poor outcome of high-grade gliomas result from the tumour relentless invasion. miR-29a/b/c downexpressions contribute to several human tumourigenesis. However, their relevance to prognosis and invasion in gliomas remains unclear. Methods: Relationships of miR-29a/b/c and CDC42 expressions to grade and survival-time in 147 human gliomas were analysed by in situ hybridisation and immunohistochemistry. Dual-luciferase reporter assay was used to identify CDC42 as a target of miR-29a/b/c. Underlining mechanisms by which miR-29a/b/c inhibited glioma cell migration and invasion were studied by in vitro and in vivo assays. Results: miR-29a/b/c expressions were inversely correlated with glioma grades, but positively correlated with patients' survival. Two distinct subgroups of grade I-IV glioma patients with different prognoses were identified according to miR-29a/b/c expressions. miR-29a/b/c overexpressions suppressed glioma cell migration and invasion through targeting CDC42 and subsequently decreasing phosphorylated PAK1/2/3, LIMK1/2 and cofilin, the pivotal downstream effectors of CDC42. Moreover, CDC42 expression was positively correlated with glioma grades, but inversely correlated with miR-29a/b/c expressions and patients' survival. In glioblastoma cell lines, CDC42-knockdown could mimic the anti-tumour effects of miR-29a/b/c. Conclusions: miR-29a/b/c are important tumour suppressors and novel prognostic biomarkers of gliomas, and miR-29a/b/c and CDC42 are potential therapeutic candidates for malignant gliomas.
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