Long noncoding RNA LEF1‐AS1 silencing suppresses the initiation and development of prostate cancer by acting as a molecular sponge of miR‐330‐5p via LEF1 repression

• Published in: Journal of cellular physiology 2019-08, Vol.234 (8), p.12727-12744
• Main Authors: Liu, Da‐Chuang, Song, Lin‐Lin, Liang, Qing, Hao, Lin, Zhang, Zhi‐Guo, Han, Cong‐Hui
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Animals; Antisense RNA; Binding; Chromosome 5; Circuits; Coupling (molecular); Crosstalk; DNA microarrays; epithelial–mesenchymal transition; Gene Expression Regulation, Neoplastic; Humans; invasion; LEF1; long noncoding RNA LEF1‐AS1; Lymph nodes; Lymphoid Enhancer-Binding Factor 1 - genetics; Lymphoid Enhancer-Binding Factor 1 - metabolism; Male; Mesenchyme; Metastases; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; microRNA‐330‐5p; Middle Aged; migration; miRNA; Neoplasms, Experimental; Prostate cancer; Prostatic Neoplasms - prevention & control; Ribonucleic acid; RNA; RNA Interference; RNA, Long Noncoding; RNA-mediated interference; Transfection; Tumorigenesis
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27893

Prostate cancer (PCa) is one of the major cancers affecting males with high mortality around the world. Recent studies have found that some long noncoding RNAs play a critical part in the cellular processes of PCa. In our study, aberrant expressed lymphoid enhancer‐binding factor‐1 antisense RNA 1 (LEF1‐AS1), microRNA‐330‐5p (miR‐330‐5p), and lymphoid enhancer‐binding factor‐1 (LEF1) were screened out from a microarray database, the role of the novel noncoding RNA regulatory circuitry in the initiation and development of PCa was investigated. LEF1‐AS1 and LEF1 were highly expressed while miR‐330‐5p was poorly expressed in PCa. Following that, the PCa PC‐3 cell line was adopted for subsequently experiments, in which the expression of LEF1‐AS1 and miR‐330‐5p was subsequently altered by means of exogenous transfection. After that, the effects of up‐ or downregulation of LEF1‐AS1 and miR‐330‐5p on epithelial–mesenchymal transition (EMT) and the cell ability for proliferation, invasion, migration in vitro, and tumorigenesis and lymph node metastasis (LNM) in vivo were evaluated. RNA crosstalk revealed that LEF1‐AS1 bound to miR‐330‐5p and LEF1 was the target gene of miR‐330‐5p. Silenced LEF1‐AS1 or elevated miR‐330‐5p exhibited inhibited EMT processes, reduced ability of proliferation, invasion and migration, coupling with decreased tumorigenesis and LNM in nude mice. The key findings of this study collectively propose downregulation of LEF1‐AS1 competing with miR‐330‐5p to inhibit EMT, invasion and migration of PCa by LEF1 repression. Downregulation of lymphoid enhancer‐binding factor‐1 antisense RNA 1 competing with miR‐330‐5p to inhibit epithelial–mesenchymal transition, invasion and migration of prostate cancer by lymphoid enhancer‐binding factor‐1 repression