title: XIAP 3'-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p.
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.
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.|Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.|Department of Pathology, Anhui Provincial Cancer Hospital, Hefei, Anhui, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Tao
authors.affiliation: Laboratory of Pathogenic Microbiology and Immunology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Mou
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.
authors.forename: Xing-Wang
authors.initials: XW
authors.lastname: Cheng
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Wen-Yong
authors.initials: WY
authors.lastname: Wu
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.|Department of Pathology, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Zheng-Sheng
authors.initials: ZS
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; C502658:FSCN1 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human
keywords: 3'UTR; XIAP; breast cancer; miRNA