LncRNA, CRNDE promotes osteosarcoma cell proliferation, invasion and migration by regulating Notch1 signaling and epithelial-mesenchymal transition.

Abstract

Osteosarcoma is the most common bone malignancy in adolescence. Recently, the long non-coding RNAs (lncRNAs) were reported to play important roles in osteosarcoma progression. The present study examined the potential role of the lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE) and molecular mechanisms underlying osteosarcoma progression. In the present study, we identified that CRNDE was up-regulated in osteosarcoma tissues and cell lines, and CRNDE expression level was significantly higher in osteosarcoma tissues from patients with advanced stage and metastasis. Overexpression of CRNDE promoted cell growth, cell proliferation, cell invasion and migration, and increased cell population at S phase with a decreased cell population at G0/G1 phase in MG-63 cells. Knock-down of CRNDE suppressed cell growth, cell proliferation, cell invasion and migration, and decreased cell population at S phase with an increased cell population at G0/G1 phase in U2OS cells. Overexpression of CRNDE was found to enhance the activity of Notch1 signaling and promote epithelial-mesenchymal transition (EMT) in MG-63 cells, while knock-down of CRNDE exerted the opposite effects in U2OS cells. The in vivo results showed that knock-down of CRNDE suppressed the tumor growth in the nude mice inoculated with osteosarcoma cells, and knock-down of CRNDE also suppressed the mRNA expression of Notch1, JAG1, N-cadherin, vimentin, and increased the mRNA expression of E-cadherin in the tumor tissues. Collectively, our results indicated that CRNDE functioned as an oncogene in osteosarcoma cell lines, and CRNDE may exert its oncogenic role via regulating Notch1 signaling and EMT in osteosarcoma.

• Authors: Zheng Li, Yonghua Tang, Wujun Xing, Wei Dong, Zhichou Wang
• Journal: Experimental and molecular pathology (Exp Mol Pathol) Vol. 104 Issue 1 Pg. 19-25 (02 2018) ISSN: 1096-0945 [Electronic] Netherlands
• PMID: 29246789 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• CRNDE RNA, human
• NOTCH1 protein, human
• RNA, Long Noncoding
• Receptor, Notch1

Topics

• Animals
• Bone Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• HEK293 Cells
• Heterografts
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Osteosarcoma (genetics, metabolism, pathology)
• RNA, Long Noncoding (genetics, metabolism)
• Receptor, Notch1 (genetics, metabolism)
• Signal Transduction
• Up-Regulation