Abstract
Long non-coding RNAs (lncRNAs) are being found to play an increasingly important role in the development of tumors. However, their biological functions and the underlying mechanisms remain unclear. Using information from GEO Datasets, we found that the lncRNA LINC00588 was downregulated in osteosarcoma (OS) in bone but was upregulated in the metastatic tumor present in the lung. We assessed the function of LINC00588 using both overexpression and knock-out studies. We performed colony formation assay, CCK-8 assay, flow cytometry, wound healing assay, transwell assay, and RT-qPCR assay and used a xenograft model to investigate the influence of LINC00588 on cell proliferation, viability, cell apoptosis and cycle, migration, invasion, endothelial cell function, EMT (epithelial to mesenchymal transition), and tumor growth, respectively. Overexpression of LINC00588 appeared to inhibit cell proliferation, viability, migration, invasion, endothelial cell function, EMT, and tumor growth but not apoptosis, while we got the opposite result when we knocked down LINC00588. Next, we predicted that LINC00588 bound to miRNA-1972 and significantly downregulated its expression, which we then verified through a luciferase reporter assay. Subsequently, we knocked down miR1972 and performed CCK-8 and transwell assays to demonstrate that downregulation of miRNA-1972 could substantially inhibit the viability and invasion of osteosarcoma cells. The expression of TP53 was downregulated at the protein level but not at the mRNA level after the overexpression of miRNA-1972. Taken together, our findings indicate that LINC00588 plays a role in OS development by downregulating the expression of miRNA-1972, which can, in turn, inhibit the expression of TP53. Hence, we believe that the LINC00588/miRNA-1072/TP53 axis could potentially serve as a therapeutic target or diagnostic biomarker for osteosarcoma.
Highlights
Osteosarcoma (OS) is the most common primary cancer of the bone that occurs mainly in children and adolescents (Ritter and Bielack, 2010; Gianferante et al, 2017)
Since long non-coding RNA (lncRNA) were found to be involved in the process of tumorigenesis, the role of the lncRNAs in OS has been intensively studied
It was shown that a few lncRNAs are abnormally expressed in osteosarcoma (Li et al, 2013; Li et al, 2016)
Summary
Osteosarcoma (OS) is the most common primary cancer of the bone that occurs mainly in children and adolescents (Ritter and Bielack, 2010; Gianferante et al, 2017). It is derived from and defined by the presence of malignant mesenchymal cells that produce osteoid and/or immature bones (Arndt et al, 2012). The role of lncRNAs in osteosarcoma pathogenesis has attracted much attention and is being heavily investigated, through high-throughput sequencing. Several lncRNAs are being actively investigated as prognostic markers for this disease (Chen et al, 2018; Zhang et al, 2018)
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