LSAMP-AS1 binds to microRNA-183–5p to suppress the progression of prostate cancer by up-regulating the tumor suppressor DCN

Background: : Prostate cancer (PCa) is a leading cause of cancer-related death in males. Aberrant expression of long noncoding RNAs (lncRNAs) is frequently reported in human malignancies. This study was performed to explore the role of LSAMP-AS1 in epithelial-mesenchymal transition (EMT), proliferat...

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Veröffentlicht in:EBioMedicine 2019-12, Vol.50, p.178-190
Hauptverfasser: Hua, Xing, Liu, Zhen, Zhou, Min, Tian, Yan, Zhao, Pei-Pei, Pan, Wen-Hai, Li, Chao-Xia, Huang, Xiao-Xiao, Liao, Ze-Xiao, Xian, Qi, Chen, Bo, Hu, Yue, Leng, Lei, Fang, Xiao-Wei, Yu, Li-Na
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Sprache:eng
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Zusammenfassung:Background: : Prostate cancer (PCa) is a leading cause of cancer-related death in males. Aberrant expression of long noncoding RNAs (lncRNAs) is frequently reported in human malignancies. This study was performed to explore the role of LSAMP-AS1 in epithelial-mesenchymal transition (EMT), proliferation, migration and invasion of PCa cells. Methods: : Initially, the differentially expressed lncRNAs in PCa were screened out by microarray analysis. The clinicopathological and prognostic significance of LSAMP-AS1 was evaluated. LSAMP-AS1 was over-expressed or silenced to investigate the roles in EMT, proliferation, migration and invasion of PCa cells. Moreover, the relationships between LSAMP-AS1 and miR-183–5p, as well as miR-183–5p and decorin (DCN) were characterized. The tumorigenicity of PCa cells was verified in nude mice. Results: : LSAMP-AS1 was poorly expressed in PCa tissues and cells. Low expression of LSAMP-AS1 was indicative of poor overall survival and disease-free survival, and related to Gleason score, TNM stage, and risk stratification. Over-expressed LSAMP-AS1 inhibited EMT, proliferation, migration and invasion of PCa cells, as well as tumor growth in nude mice. Meanwhile, over-expression of LSAMP-AS1 resulted in up-regulation of E-cadherin and down-regulation of Vimentin, N-cadherin, Ki67, PCNA, MMP-2, MMP-9, Ezrin and Fascin. Notably, LSAMP-AS1 competitively bound to miR-183–5p which directly targets DCN. It was confirmed that the inhibitory effect of LSAMP-AS1 on PCa cells was achieved by binding to miR-183–5p, thus promoting the expression of DCN. Conclusion: : LSAMP-AS1 up-regulates the DCN gene by competitively binding to miR-183–5p, thus inhibiting EMT, proliferation, migration and invasion of PCa cells. Keywords: Prostate cancer, LSAMP-AS1, MicroRNA-183–5p, Decorin, Epithelial-mesenchymal transition, Proliferation, Migration
ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2019.10.009