Circular RNA hsa_circ_0032463 Acts as the Tumor Promoter in Osteosarcoma by Regulating the MicroRNA 498/LEF1 Axis

环状 RNA hsa_circ_0032463 通过调控 MicroRNA 498/LEF1 轴在骨肉瘤中发挥肿瘤促进作用

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作者:Guanghua Qin, Xuejian Wu

Abstract

Several studies have examined the relationship between osteosarcoma (OS) and microRNAs (miRNAs). However, only a few researchers have investigated the underlying mechanism of circular RNAs (circRNAs) in OS development. Our paper aimed to assess how hsa_circ_0032463 (abbreviated "circ_0032463" here) initiates and regulates OS progression. We detected circ_0032463 expression in OS tissues and cell lines by using reverse transcription-quantitative PCR (RT-qPCR) analysis and then investigated the interaction between circ_0032463, miRNA 489 (miR-498), and LEF1 using RNA pulldown, RNA immunoprecipitation (RIP), and luciferase assays. The effect of the circ_0032463/miR-498/LEF1 axis on the migration, proliferation, and apoptosis levels of OS cells was explored using CCK-8, bromodeoxyuridine (BrdU), wound healing, and fluorescein isothiocyanate (FITC) assays. Our findings revealed that circ_0032463 expression was upregulated in OS tissues and cell lines. We also found that circ_0032463 interacted with miR-498, thereby reducing the expression of miR-498 in OS cells. Experimental results indicated that miR-498 could directly target LEF1 in OS cells and that circ_0032463 could abrogate the tumor-inhibitory effect of miR-498 by upregulating LEF1 in OS. More specifically, by binding to miR-498 and inhibiting LEF1 expression, circ_0032463 promoted the migration and proliferation abilities of OS cells and suppressed the apoptosis ability of OS cells. Overall, this research suggested that circ_0032463 could promote OS development by regulating the miR-498/LEF1 axis.

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