Silencing of HuR Inhibits Osteosarcoma Cell Epithelial-Mesenchymal Transition via AGO2 in Association With Long Non-Coding RNA XIST.

Silencing of HuR Inhibits Osteosarcoma Cell Epithelial-Mesenchymal Transition via AGO2 in Association With Long Non-Coding RNA XIST.
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HuR 沉默通过与长非编码 RNA XIST 相关的 AGO2 抑制骨肉瘤细胞上皮-间质转化。

DOI:
10.3389/fonc.2021.601982
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发表时间:
2021
影响因子:
4.7
通讯作者:
Zhuang R
Zhuang R
中科院分区:
医学3区
文献类型:
--
作者:
Liu Y;Zhang Y;Zhang J;Ma J;Xu X;Wang Y;Zhou Z;Jiang D;Shen S;Ding Y;Zhou Y;Zhuang R

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骨肉瘤是一种高度恶性、侵袭性的骨肿瘤。本研究采用免疫组化和Western blotting方法检测人抗原R(human antigen R,HuR)在骨肉瘤组织和细胞中的表达水平,探讨HuR在骨肉瘤发生发展中的作用机制。将HuR siRNA转染SJSA-1 OS细胞,下调HuR表达,观察细胞增殖、迁移和上皮间质转化(EMT)情况。进行RNA免疫沉淀以确定长非编码RNA(lncRNA)XIST和argonaute RISC催化组分(AGO)2与HuR的缔合。荧光原位杂交检测lncRNA XIST的表达。Western blotting和免疫荧光法检测HuR或/和lncRNA XIST敲低后AGO 2的表达。HuR的敲低抑制OS细胞迁移和EMT。AGO 2被鉴定为HuR的靶标,并且HuR的沉默降低AGO 2的表达。lncRNA XIST与HuR介导的AGO 2抑制相关。此外,AGO 2的敲低显着抑制细胞增殖,迁移,和EMT在OS。我们的研究结果表明,HuR敲低抑制OS细胞EMT通过调节lncRNA XIST/AGO 2信号。
Osteosarcoma (OS) is a highly malignant and aggressive bone tumor. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS. HuR expression levels in OS tissues and cells were detected by immunohistochemistry and western blotting. HuR siRNA was transfected into SJSA-1 OS cells to downregulate HuR expression, and then cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated. RNA immunoprecipitation was performed to determine the association of the long non-coding RNA (lncRNA) XIST and argonaute RISC catalytic component (AGO) 2 with HuR. Fluorescence in situ hybridization analysis was performed to detect the expression of lncRNA XIST. Western blotting and immunofluorescence assays were performed to observe AGO2 expression after HuR or/and lncRNA XIST knockdown. Knockdown of HuR repressed OS cell migration and EMT. AGO2 was identified as a target of HuR and silencing of HuR decreased AGO2 expression. The lncRNA XIST was associated with HuR-mediated AGO2 suppression. Moreover, knockdown of AGO2 significantly inhibited cell proliferation, migration, and EMT in OS. Our findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.
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