AUTHOR=Liu Yongming , Zhang Yuan , Zhang Jinxue , Ma Jingchang , Xu Xuexue , Wang Yuling , Zhou Ziqing , Jiang Dongxu , Shen Shen , Ding Yong , Zhou Yong , Zhuang Ran TITLE=Silencing of HuR Inhibits Osteosarcoma Cell Epithelial-Mesenchymal Transition via AGO2 in Association With Long Non-Coding RNA XIST JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.601982 DOI=10.3389/fonc.2021.601982 ISSN=2234-943X ABSTRACT=Background

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.

Methods

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.

Results

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.

Conclusion

Our findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.