XIAP 3'-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p

// Qiang Wu 1, 2, * , Hong Yan 1, 3, * , Si-Qi Tao 2 , Xiao-Nan Wang 4 , Lang Mou 2 , Ping Chen 2 , Xing-Wang Cheng 5 , Wen-Yong Wu 6 , Zheng-Sheng Wu 1, 2 1 Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China 2 Department of Pathology, Anhui Medical University, Hefei, Anhui, China 3 Department of Pathology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China 4 Laboratory of Pathogenic Microbiology and Immunology, Anhui Medical University, Hefei, Anhui, China 5 Department of Emergency, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China 6 Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China * These authors contributed equally to this work Correspondence to: Zheng-Sheng Wu, email: woozson@yahoo.com Keywords: XIAP, 3'UTR, miRNA, breast cancer Received: June 09, 2016      Accepted: January 23, 2017      Published: February 07, 2017 ABSTRACT The non-coding 3'-untranslated region (UTR) of genes play an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Herein, we report that ectopic expression of XIAP 3'UTR increased human breast cancer cells proliferation, colony formation, migration, invasion and xenograft tumor growth and suppressed tumor cell death. To investigate this process, we further correlated the genome-wide transcriptional profiling with the gene expression alterations after transfecting XIAP 3'UTR in MCF-7 cells. We identified a robust, genome-wide mechanism of cell migration, motility and epithelial to mesenchymal transition by which mediated by a previously described cellular component movement factor FSCN1. Expression of XIAP and FSCN1 were up-regulated synergistically after transfecting XIAP 3'UTR in vitro and in vivo . Interactions between XIAP and FSCN1 appear to be a key determinant of these processes. Co-transfection with Dicer siRNA reversed the XIAP 3'UTR-mediated oncogenicity, suggesting the miRNAs might be involved in that process. Furthermore, we demonstrated that one miRNA, miR-29a-5p, can bind to both the XIAP and FSCN1 3'UTRs and play an important role in that interactions. We showed that the 3'UTR of XIAP was able to antagonize miR-29a-5p, and resulted in the increased translation of XIAP and FSCN1. Thus, our findings reveal important new insights into how XIAP 3'UTR works, suggesting that the non-coding XIAP 3'UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by which XIAP 3'UTR frees the target mRNAs from being repressed.