Interplay between PCBP2 and miRNA modulates ARHGDIA expression and function in glioma migration and invasion.
Interplay between PCBP2 and miRNA modulates ARHGDIA expression and function in glioma migration and invasion.
复制标题
PCBP2 和 miRNA 之间的相互作用调节神经胶质瘤迁移和侵袭中 AHGDIA 的表达和功能
DOI：
10.18632/oncotarget.6869
复制
发表时间：
2016-04-12
期刊：
影响因子：
--
通讯作者：
Han W
中科院分区：
文献类型：
--
作者：
Lin X;Yang B;Liu W;Tan X;Wu F;Hu P;Jiang T;Bao Z;Yuan J;Qiang B;Peng X;Han W
RNA-RNA和蛋白- rna相互作用对正常发育的转录后调控至关重要，在癌症的发生和发展中可能不受调控。rna结合蛋白PCBP2是人类恶性胶质瘤的一种致癌蛋白，是mRNA和miRNA生物发生、稳定性和活性的重要调节因子。在这里，我们发现Rho GDP解离抑制剂α (ARHGDIA)是结合PCBP2的靶mRNA，并通过体外和体内EMT和转移模型的分析揭示了ARHGDIA作为推定的转移抑制因子的作用。此外，我们证明ARHGDIA是胶质瘤中miR-151-5p和miR-16的潜在靶点。PCBP2与ARHGDIA mRNA的3'UTR之间的相互作用可能诱导RNA结构的局部变化，有利于随后miR-151-5p和miR-16的结合，从而导致ARHGDIA表达的抑制。PCBP2可能通过减轻ARHGDIA的功能，促进miR-151-5p和miR-16促进胶质瘤细胞迁移和侵袭。
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.