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

// Xihua Lin 1 , Bin Yang 1 , Wei Liu 1 , Xiaochao Tan 3 , Fan Wu 1 , Peishan Hu 1 , Tao Jiang 2 , Zhaoshi Bao 2 , Jiangang Yuan 1 , Boqin Qiang 1 , Xiaozhong Peng 1 and Wei Han 1 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China 2 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 3 Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to: Wei Han, email: // Xiaozhong Peng, email: // Keywords : PCBP2, ARHGDIA, miRNA, glioma, migration and invasion Received : September 01, 2015 Accepted : January 03, 2016 Published : January 09, 2016 Abstract RNA-RNA and protein-RNA interactions are essential for post-transcriptional regulationin normal development and may be deregulated in cancer initiation and progression. The RNA-binding protein PCBP2, 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 α (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.