LncRNA DLEU2 promotes tumour growth by sponging miR-337-3p in human osteosarcoma.

Abstract

According to statistics, abnormal regulation of lncRNAs pivotally influences multiple malignant tumours. DLEU2, as one of these lncRNAs, is detected to be related to growth and development of tumours. The molecular mechanisms of DLEU2 in osteosarcoma, however, are still unknown. QRT-PCR was adopted to analyse the correlations of clinicopathological features and prognosis of osteosarcoma cases with DLEU2. The influences of DLEU2 on cell migration and viability were evaluated independently by experiments in vitro and in vivo. Bioinformatics analysis, RNA immunoprecipitation (RIP) assay, and dual luciferase reporter gene assay confirmed the specific binding of DLEU2 to miR-337-3p. Moreover, rescue experiments were carried out to further evaluate the regulatory association between miR-337-3p expression and DLEU2. In osteosarcoma tissues and cells, DLEU2 expression level was raised remarkably in comparison with that in para-carcinoma normal tissues, and DLEU2 high expression had associations with poor prognosis, tumour stages, and TS of osteosarcoma cases. Cell migration ability and viability were blocked by DLEU2 knockdown but enhanced by ectopic DLEU2 expression in vitro and in vivo. Additionally, DLEU2 was found to sponge miR-337-3p and trigger the stimulating effect in osteosarcoma cells, which would be suppressed by miR-337-3p mimics. Furthermore, a negative correlation existed between miR-337-3p expression and DLEU2 in osteosarcoma tissues. This study manifests that DLEU2 sponges miR-337-3p to accelerate tumour growth and is confirmed to be a factor for poor prognosis of osteosarcoma cases. SIGNIFICANCE OF THE STUDY: LncRNA DLEU2 has been reported to be dysregulated in many tumours; however, the functions and underlying mechanism of DLEU2 in osteosarcoma pathogenesis are still unknown. This study is the first to demonstrate the roles of DLEU2 in osteosarcoma and revealed that DLEU2 may serve as a ceRNA to sponge miR-337-3p and then promote the progression of osteosarcoma, providing a potential therapeutic target for osteosarcoma.

• Authors: Wei Liu, Peng-Cheng Liu, Ke Ma, Yuan-Yi Wang, Qing-Bao Chi, Ming Yan
• Journal: Cell biochemistry and function (Cell Biochem Funct) Vol. 38 Issue 7 Pg. 886-894 (Oct 2020) ISSN: 1099-0844 [Electronic] England
• PMID: 32196715 (Publication Type: Journal Article)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• Antagomirs
• DLEU2 lncRNA, human
• MicroRNAs
• Mirn337 microRNA, human
• RNA, Long Noncoding
• RNA, Small Interfering

Topics

• Animals
• Antagomirs (metabolism)
• Area Under Curve
• Base Sequence
• Bone Neoplasms (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Humans
• Mice
• Mice, Nude
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• Osteosarcoma (drug therapy, genetics, pathology)
• RNA Interference
• RNA, Long Noncoding (antagonists & inhibitors, genetics, metabolism)
• RNA, Small Interfering (metabolism, therapeutic use)
• ROC Curve
• Sequence Alignment
• Transplantation, Heterologous