LINC01128 regulates the development of osteosarcoma by sponging miR-299-3p to mediate MMP2 expression and activating Wnt/β-catenin signalling pathway.

Abstract

Osteosarcoma (OS) is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. The important role of long non-coding RNAs (lncRNAs) in the biological processes of OS has been demonstrated through several studies. In the current study, we evaluated the role of the lncRNA, LINC01128, in OS. We analysed the expression of LINC01128 in three OS gene expression omnibus (GEO) data sets GSE21257, GSE36001 and GSE42352. The expression of LINC01128 in OS tissues and matched non-tumour tissues obtained from 50 OS patients was detected using qRT-PCR. The association between LINC01128 expression and overall survival of OS patients was evaluated using the Kaplan-Meier method. The effects of LINC01128 knockdown and overexpression were evaluated through in vitro and in vivo assays. The LINC01128/miR-299-3p/ MMP2 axis was verified using dual-luciferase reporter assay and qRT-PCR assays. GEO data sets analysis revealed that the expression of LINC01128 was increased in OS. Elevated LINC01128 expression was accompanied by shorter overall survival in OS patients. Functional studies revealed that LINC01128 knockdown reduced the proliferation, migration and invasion of OS cells both in vitro and in vivo. Mechanistically, LINC01128 sponged miR-299-3p to increase MMP2 expression. Rescue assays determined the role of the LINC01128/miR-299-3p/MMP2 axis in the proliferation, migration and invasion of OS cells. Additionally, the Wnt/β-catenin signalling pathway was activated by LINC01128 and MMP2 in OS cell lines. In summary, this study demonstrates that LINC01128 facilitates OS by functioning as a sponge of miR-299-3p, thus promoting MMP2 expression and activating the Wnt/β-catenin signalling pathway.

• Authors: Qiang Yao, Ting Chen
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 24 Pg. 14293-14305 (12 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 33108067 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• MIRN299 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Adolescent
• Animals
• Bone Neoplasms (genetics, metabolism, mortality, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Child
• Disease Models, Animal
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• Humans
• Male
• Matrix Metalloproteinase 2 (genetics)
• Mice
• MicroRNAs (genetics)
• Neoplasm Staging
• Osteosarcoma (genetics, metabolism, mortality, pathology)
• Prognosis
• RNA Interference
• RNA, Long Noncoding (genetics)
• Tumor Burden
• Wnt Signaling Pathway
• Xenograft Model Antitumor Assays
• Young Adult