LncRNA NR_136400 Suppresses Cell Proliferation and Invasion by Acting as a ceRNA of TUSC5 That Is Modulated by miR-8081 in Osteosarcoma

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.

Expression of E-cadherin and N-cadherin in Epithelial-to-Mesenchymal Transition of Osteosarcoma: A Systematic Review

“…Lipofectamine series 2000 and 3000 have been listed as a common method which includes a lipid vector and a CRISPR component for transcript editing [ 2 , 4 ]. A lentiviral vector was also used with puromycin resistance for cell selection [ 14 , 16 , 27 ]. Luciferase assay with radioactive ligands can be used to confirm the expression of desired plasmid products [ 2 , 4 ].…”

“…Previous studies have utilized a surrogate measurement of E-cadherin and N-cadherin by evaluating tumor expression of miRNAs, long noncoding RNAs (lnRNAs), exosomes, or other RNA fragments, however, direct serum measurement of E-cadherin may offer greater insight on malignancy potential than upstream effector molecules [ 9 , 45 ]. This vastness of RNA components affecting gene expression has been termed the tumor competing endogenous RNA (ceRNA) [ 14 ]. Interruption of the tumor ceRNA leads to the desired phenotype of experiments with reduced invasiveness and growth of osteosarcoma cells [ 14 ].…”

“…A complex web of signaling pathways known to downregulate E-cadherin expression and upregulate mesenchymal markers is involved in mediating EMT [ 13 ]. Additionally, new research has emphasized how microRNAs modulate EMT in osteosarcoma [ 14 ].…”

Oncogenic functions of ZEB1 in pediatric solid cancers: interplays with microRNAs and long noncoding RNAs

“…The mechanisms mediating LINC00612 actions include EMT resulting from increased ZEB1 expression [97]. Downregulation of the lncRNA NR_136400 induces osteosarcoma cell proliferation, apoptosis, and invasion, and stimulates EMT partially by binding miR-8081 and enhancing ZEB1 expression [98].…”

Lnc-CLSTN2-1:1 Promotes Osteosarcoma Progression by Disrupting Redox Balance through PI3K/AKT Signaling Pathway

“…For example, LncRNA BE503655 inhibits proliferation, invasion, and migration of osteosarcoma through the Wnt/β-catenin pathway 17 , whereas Shen et al 10 discovered that lncRNA KCNQ1OT1 sponges miR-34c-5p and promotes osteosarcoma development by enhancing aerobic glycolysis through ALDOA. Liu et al 18 discovered that by functioning as a ceRNA for TUSC5, the lncRNA NR 136400 inhibits cell growth and invasion, which is under the control of miR-8081 in osteosarcoma. Lnc-CLSTN2-1:1 is aberrantly expressed in osteosarcoma cells; however, its biological activity has not yet been described.…”