Abstract
BackgroundOsteosarcoma (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.MethodsHuR 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.ResultsKnockdown 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.ConclusionOur findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.
Highlights
Osteosarcoma (OS), which mainly occurs in children and young adults, is one of the most prevalent malignant cancers, has a low survival rate, and poor overall prognosis
The results indicate that human antigen R (HuR) binds to the long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) and argonaute RISC catalytic component 2 (AGO2) in OS cells
Considering that AGO2 was significantly regulated by HuR/ lncRNA XIST, we further evaluated the role of AGO2 in OS cells
Summary
Osteosarcoma (OS), which mainly occurs in children and young adults, is one of the most prevalent malignant cancers, has a low survival rate, and poor overall prognosis. Studies are needed to explore the underlying molecular mechanisms involved in OS carcinogenesis, progression, and metastasis to find out potential therapeutic targets. RNA-binding protein HuR (human antigen R), known as ELAVL1 (ELAV-like RNA-binding protein 1), binds to elements rich in adenylate and uridylate (AU-rich elements) to regulate the stability and translation of various mRNAs [3, 4]. Because of its pivotal role in stabilizing the mRNA of key factors involved in carcinogenesis, the effects and therapeutic potential of HuR in cancer have been intensively investigated [5]. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS
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