Abstract
Long non-coding RNAs (lncRNAs) are emerging as important regulators of the processes involved in cancer development and progression. The molecular mechanism by which lncRNAs regulate the progression of osteosarcoma has not been clearly elucidated. The role of NR_136400, which is an uncharacterized lncRNA, has not been previously reported in osteosarcoma (OS). In the present study, we demonstrated that NR_136400 was downregulated in OS cells and that its downregulation promoted OS cell proliferation, apoptosis, and invasion. NR_136400 downregulation facilitated EMT by inhibiting the expression of E-cadherin and elevating the expression of ZEB1, Snail, and fibronectin. In vivo experiments using a xenograft tumor mouse model revealed that NR_136400 downregulation promoted tumor growth in OS. Mechanistic investigations demonstrated that NR_136400 competitively bound to miR-8081 and then upregulated the protein expression of TUSC5. Taken together, a newly identified regulatory mechanism of the lncRNA NR_136400/miR-8081/TUSC5 axis was systematically studied in OS, providing a promising target for therapeutic treatment.
Highlights
Osteosarcoma (OS) is a highly malignant bone cancer that originates from bone marrow mesenchymal stem cells
This study identified Long non-coding RNAs (lncRNAs) NR_136400, which was uncharacterized in the past, and investigated its biological function in OS cells and the mechanism by which it suppresses cell proliferation and invasion; it was found that lncRNA NR_136400 acts as a competing endogenous RNA (ceRNA) of TUSC5 that is modulated by miR-8081 to regulate OS formation and progression
Zhu et al (2019) reported that the long noncoding RNA CTC-297N7.9 was downregulated in hepatocellular carcinoma and predicted poor prognosis in these patients
Summary
Osteosarcoma (OS) is a highly malignant bone cancer that originates from bone marrow mesenchymal stem cells. LncRNAs play a vital role in regulating the expression of genes by mediating their transcription, translation, and protein functions (Wang and Chang, 2011; Hu et al, 2018; Begolli et al, 2019). The expression of miRNAs in tumors and its implications in the regulation of tumorigenesis and in the early detection, treatment, and prognosis of tumors have been hot topics in cancer research (Zhang et al, 2015). This study identified lncRNA NR_136400, which was uncharacterized in the past, and investigated its biological function in OS cells and the mechanism by which it suppresses cell proliferation and invasion; it was found that lncRNA NR_136400 acts as a ceRNA of TUSC5 that is modulated by miR-8081 to regulate OS formation and progression
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