Abstract
As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. Nevertheless, how circRNAs participate in osteosarcoma (OS) development and progression are not well understood. In the present study, we identified a circRNA circFAT1(e2) with an upregulated expression level in OS tissues. By functional experiments, we found that circFAT1(e2) depletion significantly suppressed the proliferation and reduced migration in OS. In terms of mechanism, we found that circFAT1(e2) inhibited miR-181b, while miR-181b targeted HK2. By releasing the inhibition of miR-181b on HK2 expression, leading to attenuated OS progression. Mechanistic investigations suggested that circFAT1(e2) served as a competing endogenous RNA (ceRNA) of miR-181b to enhance HK2 expression. On the whole, our study indicated that circFAT1(e2) exerted oncogenic roles in OS and suggested the circFAT1(e2)/miR-181b/HK2 axis might be a potential therapeutic target.
Highlights
Eukaryotes contain a large number of noncoding RNA [1]
CircANKS1B can use miR-148a-3p and miR-152-3p to increase the expression of the transcription factor USF1, thereby upregulating the expression of TGF-β1, which in turn activates TGF-β1/Smad signaling to promote epithelial-mesenchymal Transformation (EMT), thereby promoting the invasion and metastasis of breast cancer [11]
We further found that circFAT1(e2) can sponge miR-181b to reduce the expression of miR-181b, leading to the dysregulation of Human glandular kallikrein2 (HK2) and promoting osteosarcoma cell growth
Summary
Eukaryotes contain a large number of noncoding RNA [1] They are not directly involved in the process of protein translation as templates, noncoding RNAs are found to play crucial roles in modulating cancer proliferation, migration, and invasion. Noncoding RNA includes rRNA which is one of the components of the ribosome, tRNA which acts as a porter in the translation process, snRNA that regulates transcriptional activities in the nucleus, snoRNA that modifies other RNA, microRNA (miRNA) that participates in the regulation of posttranscriptional genes, and important regulators lncRNA and circRNA that are widely involved in metabolic activities [2]. The previous study found that the high-level expression of miR-145 was remarkably proved to suppress the c-Myc/eIF4E pathway and inhibiting the growth of nonsmall cell lung cancer [4]. We further found that circFAT1(e2) can sponge miR-181b to reduce the expression of miR-181b, leading to the dysregulation of HK2 and promoting osteosarcoma cell growth
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