Hsa_circ_0003732 promotes osteosarcoma cells proliferation via miR-545/CCNA2 axis.

Binjie Gui,Yingqi Feng,Mousheng Zang,Li Li,Xiang-an Kong,Yong Hu,Jisheng Dong

doi:10.1042/bsr20191552

Abstract

Osteosarcoma (OS) is a primary malignant bone tumor with a high fatality rate. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that have been verified to participate in cancer pathophysiological processes. We aim to investigate the roles of circRNAs in osteosarcoma tumorigenesis. In the present study, we showed that hsa_circ_0003732 was up-regulated in OS tissues and elevated level of hsa_circ_0003732 was linked to poor prognosis of OS patients. Functional investigation indicated that hsa_circ_0003732 promoted proliferation of OS cells. Furthermore, we identified miR-545 as the hsa_circ_0003732-associated microRNA and CCNA2 was a direct target of miR-545. In addition, hsa_circ_0003732 could elevate CCNA2 expression via miR-545, resulting in the promotion of OS cells proliferation. Altogether, our findings demonstrate that hsa_circ_0003732 promotes OS cells proliferation via miR-545/CCNA2 axis and imply hsa_circ_0003732 may be a potential prognosis biomarker and therapeutic target for OS.

Highlights

Osteosarcoma (OS) is the most common bone malignancy that usually occurs in young people [1]
Total RNA was extracted from three pairs of OS tissues and adjacent noncancerous tissue (ANT) and digested with Rnase R (Epicentre, Inc.) to increase the enrichment of circular RNA (circRNA). circRNA microArray was performed using circRNA chip provided by Arraystar containing the specific probes for human circRNA
We found that hsa circ 0003732 expression was increased in OS tissues compared with ANTs (Figure 1A)

Summary

Introduction

Osteosarcoma (OS) is the most common bone malignancy that usually occurs in young people [1]. Despite the combination of advanced treatments such as surgery, chemotherapy and radiotherapy, the prognosis of OS patients is still poor due to the rapid progression [2,3]. The poor prognosis of osteosarcoma is partially due to the lack of good molecular biomarkers at diagnosis and effective therapeutic targets in the treatment [4]. There is an urgent requirement to investigate new molecules that were involved in osteosarcoma tumorigenesis and to discover novel diagnosis biomarkers and therapeutic targets for osteosarcoma. What’s more, some studies showed that circRNAs were aberrantly express in OS and involved in osteosarcoma tumorigenesis [10,11,12,13]. CircRNAs have potential as candidates for diagnostic biomarkers and therapeutic targets in patients with OS and studying circRNAs in osteosarcoma has important clinical significance

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Conclusion