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MiR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients.


ABSTRACT:

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.

SUBMITTER: Shi C 

PROVIDER: S-EPMC5625669 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

miR-29a/b/c function as invasion suppressors for gliomas by targeting CDC42 and predict the prognosis of patients.

Shi Cuijuan C   Ren Linlin L   Sun Cuiyun C   Yu Lin L   Bian Xiuwu X   Zhou Xuexia X   Wen Yanjun Y   Hua Dan D   Zhao Shujun S   Luo Wenjun W   Wang Run R   Rao Chun C   Wang Qian Q   Yu Shizhu S  

British journal of cancer 20170808 7


<h4>Background</h4>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.<h4>Methods</h4>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 CD  ...[more]

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