IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.
IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.
复制标题
DOI：
10.1016/j.celrep.2016.04.083
复制
发表时间：
2016-05-31
期刊：
影响因子：
8.8
通讯作者：
Sanford JR
中科院分区：
文献类型：
--
作者：
Ennajdaoui H;Howard JM;Sterne-Weiler T;Jahanbani F;Coyne DJ;Uren PJ;Dargyte M;Katzman S;Draper JM;Wallace A;Cazarez O;Burns SC;Qiao M;Hinck L;Smith AD;Toloue MM;Blencowe BJ;Penalva LO;Sanford JR
胰岛素样生长因子2 mRNA结合蛋白3（IGF 2BP 3）表达与恶性程度相关。但其在发病机制中的作用仍然是个谜。在这里，我们询问了IGF 2BP 3-RNA相互作用网络在胰腺导管腺癌（PDAC）细胞。使用全基因组方法的组合，我们确定了IGF 2BP 3的164个直接mRNA靶点。这些转录物编码富含细胞迁移、增殖和粘附等功能的蛋白质。IGF 2BP 3的缺失降低了PDAC细胞的侵袭力并重塑了粘着斑连接。单个核苷酸分辨率交联免疫沉淀（iCLIP）显示IGF 2BP 3和miRNA结合位点的显著重叠。IGF 2BP 3促进RNA诱导沉默复合物（RISC）与特定转录物的结合。我们的研究结果表明IGF 2BP 3通过调节miRNA-mRNA相互作用影响恶性肿瘤相关的RNA调节子。
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) expression correlates with malignancy. But its role(s) in pathogenesis remain enigmatic. Here, we interrogated the IGF2BP3-RNA interaction network in pancreatic ductal adenocarcinoma (PDAC) cells. Using a combination of genome-wide approaches we identify 164 direct mRNA targets of IGF2BP3. These transcripts encode proteins enriched for functions such as cell migration, proliferation and adhesion. Loss of IGF2BP3 reduced PDAC cell invasiveness and remodeled focal adhesion junctions. Individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) revealed significant overlap of IGF2BP3 and miRNA binding sites. IGF2BP3 promotes association of the RNA induced silencing complex (RISC) with specific transcripts. Our results show that IGF2BP3 influences a malignancy-associated RNA regulon by modulating miRNA-mRNA interactions.