Long Non-Coding Rna Zeb2-As1 Regulates Osteosarcoma Progression By Acting As A Molecular Sponge Of Mir-107 To Modulate Sall4 Expression

AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH(2021)

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摘要
Increasing evidence has confirmed long non-coding RNAs (lncRNAs) as important regulators involved in several pathophysiological processes in many diseases. The aim of this study was to investigate the roles of lncRNA ZEB2-AS1 (ZEB2-AS1) in osteosarcoma (OS). The levels of ZEB2-AS1 in OS tissues and cells were detected using RT-PCR. The clinical significance of ZEB2-AS1 expressions in OS patients was statistically analyzed. The functional effects of ZEB2-AS1 on the proliferation, apoptosis, invasion, and metastasis of OS cells was determined by a series of cellular experiments. Bioinformatic analysis, dual-luciferase reporter assays and pull-down assays were carried out for the confirmation of the molecular binding. We found that ZEB2-AS1 expression was distinctly upregulated in OS specimens and cell lines. Higher levels of ZEB2-AS1 in OS patients were associated with clinical stage, distant metastasis and unfavorable survivals. A multivariate Cox model revealed that ZEB2-AS1 expression was an independent prognostic factor for OS patients. Cellular experiments revealed that knockdown of ZEB2-AS1 inhibited proliferation and metastasis, and induced apoptosis in vitro. Mechanistic investigation revealed that ZEB2-AS1 acted as a sponge for miR-107 and blocked the inhibition of spalt like transcription factor 4 (SALL4) via miR-107 in OS cells. Rescue experiments suggested that up-regulation of ZEB2-AS1 could partly attenuate the miR-107 mediated inhibition of SALL4 expression in OS cells. To sum up, our data revealed that ZEB2-AS1 played an oncogenic role in OS progression, and could serve as a novel molecular target for treating this tumor.
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关键词
LncRNA ZEB2-AS1, miR-107, SALL4, prognosis, invasion, osteosarcoma
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