Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma

被引：33

作者：

Chen, Yan ^{[1
,2
,3
]}

Deng, Xubin ^{[4
]}

Chen, Weiquan

Shi, Pengwei ^{[5
]}

Lian, Mei ^{[2
,3
]}

Wang, Hongxiao ^{[1
]}

Wang, Kewan ^{[1
]}

Qian, Dadi ^{[1
]}

Xiao, Dong ^{[2
,3
]}

Long, Hao ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Neurosurg, Guangzhou, Guangdong, Peoples R China

[2] Southern Med Univ, Canc Res Inst, Guangdong Prov Key Lab Canc Immunotherapy Res, Guangzhou, Guangdong, Peoples R China

[3] Southern Med Univ, Canc Res Inst, Guangzhou Key Lab Tumor Immunol Res, Guangzhou, Guangdong, Peoples R China

[4] Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou, Guangdong, Peoples R China

[5] Southern Med Univ, Nanfang Hosp, Dept Emergency, Guangzhou, Guangdong, Peoples R China

来源：

CELL DEATH & DISEASE | 2019年 / 10卷 / 6期

基金：

中国国家自然科学基金;

关键词：

SPHINGOSINE KINASE ISOFORMS; BETA-CATENIN; CANCER CELLS; AKT-PATHWAY; EPIGENETIC REGULATION; MIGRATION; INVASION; PROLIFERATION; EXPRESSION; PROGNOSIS;

D O I：

10.1038/s41419-019-1671-5

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Aberrant microRNA-708 (miR-708) expression is frequently reported in cancer studies; however, its role in glioma has not been examined in detail. We investigated miR-708 function in glioma and revealed that miR-708 expression was significantly down-regulated in glioma tissues and cell lines. Restoration of miR-708 inhibited glioma cell growth and invasion both in vitro and in vivo. The oncogene SPHK2 (sphingosine kinase 2) was identified as a downstream target of miR-708 using luciferase and western blot assays. miR-708 inhibited AKT/beta-catenin signaling, which is activated by SPHK2. In addition, we revealed that miR-708 was transcriptionally repressed by EZH2 (enhancer of zeste homolog 2)-induced histone H3 lysine 27 trimethylation and promoter methylation. In summary, our findings revealed that miR-708 is a glioma tumor suppressor and suggest that miR-708 is a potential therapeutic target for glioma patients.

引用

页数：13

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