Interplay between PCBP2 and miRNA modulates ARHGDIA expression and function in glioma migration and invasion

被引:38
作者
Lin, Xihua [1 ]
Yang, Bin [1 ]
Liu, Wei [1 ]
Tan, Xiaochao [3 ]
Wu, Fan [1 ]
Hu, Peishan [1 ]
Jiang, Tao [2 ]
Bao, Zhaoshi [2 ]
Yuan, Jiangang [1 ]
Qiang, Boqin [1 ]
Peng, Xiaozhong [1 ]
Han, Wei [1 ]
机构
[1] Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Sch Basic Med, Beijing 100730, Peoples R China
[2] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China
[3] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Dept Thorac, Houston, TX 77030 USA
基金
中国国家自然科学基金;
关键词
PCBP2; ARHGDIA; miRNA; glioma; migration and invasion; EPITHELIAL-MESENCHYMAL TRANSITION; RNA-BINDING PROTEINS; RHO-GTPASES; MESSENGER-RNA; TUMOR PROGRESSION; PROSTATE-CANCER; MICRORNA; FAMILY; GROWTH; ALPHA;
D O I
10.18632/oncotarget.6869
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
RNA-RNAand protein-RNAinteractions are essential for post-transcriptionalregulationin normal development and may be deregulated in cancerinitiation and progression. The RNA-binding proteinPCBP2, an oncogenic protein in human malignant gliomas, is an essential regulator of mRNA and miRNA biogenesis, stability and activity.Here, we identified Rho GDP dissociation inhibitor a (ARHGDIA) as a target mRNA that binds to PCBP2, and we uncovered the role of ARHGDIA as a putative metastasis suppressor through analyses of in vitro and in vivo models of EMT and metastasis. Furthermore, we demonstrated that ARHGDIA is a potential target of miR-151-5p and miR-16 in gliomas. The interaction between PCBP2 and the 3'UTR of the ARHGDIA mRNA may induce a local change in RNA structure that favors subsequent binding of miR-151-5p and miR-16, thus leading to the suppression of ARHGDIA expression. PCBP2 may facilitate miR-151-5p and miR-16 promotion of glioma cell migration and invasion through mitigating the function of ARHGDIA.
引用
收藏
页码:19483 / 19498
页数:16
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