Long noncoding RNA DANCR aggravates retinoblastoma through miR-34c and miR-613 by targeting MMP-9.

Abstract

Long non-coding RNAs (lncRNAs) have been identified to play vital roles in cancers, including human retinoblastoma (RB). However, the deepgoing mechanism is still ambiguous. In present study, we investigate the biological role of lncRNA DANCR (differentiation antagonizing non-protein coding RNA) in carcinogenesis of RB. Results revealed that DANCR was up-regulated in RB tissue and cell lines. Moreover, the ectopic overexpression of DANCR indicated poor overall survivals and disease free survival (DFS) for RB patients. In vitro and in vivo experiments, DANCR knockdown suppress the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) correlated protein (N-cadherin, Vimentin) of RB cells. Bioinformatics analysis predicted that miR-34c and miR-613 targeted with 3'-UTR of DANCR, besides, miR-34c and miR-613 also targeted with 3'-UTR of MMP-9, which was validated by luciferase reporter assay. Functional experiments demonstrated that miR-34c and miR-613 could reverse the oncogenic function of DANCR in RB tumorigenesis. In conclusion, our results reveal that DANCR function as competing endogenous RNA (ceRNA) for miR-34c and miR-613 to modulate progression and metastasis in RB oncogenesis via targeting MMP-9, presenting the in-depth regulation of DANCR in RB and providing a novel insight for ceRNA mechanism for RB.

• Authors: Jing-Xian Wang, Yuan Yang, Kun Li
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 233 Issue 10 Pg. 6986-6995 (10 2018) ISSN: 1097-4652 [Electronic] United States
• PMID: 29744877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• MIRN34 microRNA, human
• MIRN613 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Apoptosis (genetics)
• Carcinogenesis (genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Epithelial-Mesenchymal Transition (physiology)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Matrix Metalloproteinase 9 (genetics, metabolism)
• MicroRNAs (genetics)
• RNA, Long Noncoding (genetics)
• Retinoblastoma (genetics)