Long noncoding RNA CRNDE activates Wnt/β-catenin signaling pathway through acting as a molecular sponge of microRNA-136 in human breast cancer.

Long non-coding RNAs (lncRNAs) serve critical roles in the tumorigenesis and development of multiple human malignancies. Herein, we aimed to explore the biological and clinical significance of lncRNA CRNDE in human breast cancer (BC). The expression of CRNDE in BC tissues and cell lines was detected, and the association between CRNDE expression and clinicopathologic features of BC patients was also analyzed. Novel targets of CRNDE were identified through a bioinformatics search and confirmed using a dual-luciferase reporter system. Gain and loss-of-function studies were carried out to verify whether CRNDE exerts its biological functions through its downstream target. CCK-8, colony formation, wound-healing, and transwell assays were applied to detect the altered phenotypes of BC cell lines in vitro after transfection. Tumor xenografts were created to detect the function of CRNDE in vivo tumorigenesis. CRNDE expression is remarkably up-regulated in BC tissue specimens and cell lines in comparison to corresponding normal tissues and normal human breast epithelial cells. Up-regulated CRNDE expression was greatly associated with larger tumor size, advanced TNM stage and unfavorable prognosis of BC patients. We uncovered that miR-136 is a bona fide binding target of CRNDE, and that up-regulation of CRNDE promoted the mRNA and protein expressions of β-catenin, c-myc and cyclinD1. Overexpressed CRNDE facilitated in vitro cell proliferation, migration and invasion of BC cells. In vivo assay showed that the average tumor volume and weight were largest in the group of CRNDE overexpression. CRNDE might hyperactivate the Wnt/β-catenin signaling pathway through directly repressing miR-136 expression in BC; CRNDE could be considered as a prognostic biomarker and therapeutic target in BC diagnosis and treatment.