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.

Comprehensive Analysis of Differentially Expressed Profiles of lncRNAs/mRNAs and miRNAs with Associated ceRNA Networks in Triple-Negative Breast Cancer

“…It has been reported that lncRNA DLX6-AS1 was up-regulated in lung adenocarcinoma (LAC) tissues compared to paired adjacent normal lung tissues and high DLX6-AS1 expression levels were significantly associated with both histological differentiation and TNM stage [41]. Recent researches have demonstrated that FSCN1, SOX11 and PSAT1 were associated with poor clinical outcome in breast cancer [42][43][44]. Our results are consistent with these reports.…”

MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells

“…miRNAs are reported to function through binding to 3’-untranslated region (3’UTR) of numerous target genes, resulting in degradation of mRNA or translation block [9, 10]. Mounting literatures have proved that miRNAs are involved in multiple diseases including MI [11-13].…”

MicroRNA-149 suppresses the proliferation and increases the sensitivity of ovarian cancer cells to cisplatin by targeting X-linked inhibitor of apoptosis

“…XIAP, as a member of the inhibitors of apoptosis family, has been reported in numerous types of human cancer, and is associated with chemical or radiation resistance (27)(28)(29)(30). Recent studies indicated that expression of XIAP may be regulated by miRNAs (31)(32)(33)(34). In the current study, it was observed that XIAP is a direct target gene of miR-149 in ovarian cancer.…”