XIAP 3'-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p
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Qiang Wu1,2,*, Hong Yan1,3,*, Si-Qi Tao2, Xiao-Nan Wang4, Lang Mou2, Ping Chen2, Xing-Wang Cheng5, Wen-Yong Wu6, Zheng-Sheng Wu1,2
1Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
2Department of Pathology, Anhui Medical University, Hefei, Anhui, China
3Department of Pathology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China
4Laboratory of Pathogenic Microbiology and Immunology, Anhui Medical University, Hefei, Anhui, China
5Department of Emergency, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
6Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
*These authors contributed equally to this work
Zheng-Sheng Wu, email: firstname.lastname@example.org
Keywords: XIAP, 3'UTR, miRNA, breast cancer
Received: June 09, 2016 Accepted: January 23, 2017 Published: February 07, 2017
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.
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