Abstract
Circular RNAs (circRNAs) are a novel class of non-coding RNA that have recently shown to have huge capabilities in the regulation of gene expression at the posttranscriptional level. Growing evidence has indicated that circRNAs could serve as competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) and suppress functions of targeted miRNAs. Osteosarcoma (OS) is the most common malignant primary bone cancer. Hsa_circ_0002137 is upregulated in OS. However, the role of hsa_circ_0002137 in OS remains unclear. Using miRNA pull-down assay, we showed that cir_0002137 sponged hsa-miR-1246, and BCL2 apoptosis regulator (BCL2) mRNA was a potential target of hsa-miR-1246 in human osteosarcoma (HOS) cells. Further, we found that hsa_cir_0002137 could enhance the expression of BCL2 hsa-miR-1246 and promote HOS cell growth through sponging hsa-miR-1246. Moreover, RNA binding protein immunoprecip itation (RIP) assay revealed that lin-28 homolog B (LIN28B) protein associated with hsa_circ_0002137, and LIN28B could increase hsa_circ_0002137 stability and thus accelerate OS cell growth. Our work was the first to study the functions of hsa_circ_0002137, has-miR-1246 and LIN28B in OS, and these results may provide novel therapeutic targets for OS treatment.
Highlights
Osteosarcoma (OS), which is characterized by high metastatic potential and poor clinical prognosis as well as high recurrence rate (Li et al, 2019; Song and Li, 2018), is widely regarded as the most common malignant primary bone cancer in children and adolescents (Li et al, 2019)
Our study revealed that hsa_circ_0002137 regulated BCL2 expression by targeting has-miR-1246 and enhanced OS cell growth
MiRNA pulldown was carried out to detect whether hsa-miR-1246 could bind to hsa_circ_0002137 and BCL2 mRNA, and the complementary binding between hsa_circ_0002137, hsamiR-1246 and BCL2 mRNA had been primarily identified by bioinformatics tools
Summary
Osteosarcoma (OS), which is characterized by high metastatic potential and poor clinical prognosis as well as high recurrence rate (Li et al, 2019; Song and Li, 2018), is widely regarded as the most common malignant primary bone cancer in children and adolescents (Li et al, 2019). In order to improve the curative ratio and prognosis of OS, it is urgent to find novel and more effective therapeutic targets with a better understanding of the molecular mechanisms that underlie the occurrence and development of OS (Li and Song, 2017). CircRNAs are novel endogenous noncoding-RNAs (Wang et al, 2019b) characterized by a covalent closed-loop structure with neither 5’ to 3’ polarity nor polyadenylated tail (Qu et al, 2015). Through the ceRNA network, circular RNA can play an important role in the development of various diseases (An et al, 2017; He et al, 2017a; Huang et al, 2016; Wang et al, 2017), including OS (Soghli et al, 2020)
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