Circ-ATAD1 is overexpressed in osteosarcoma (OS) and suppresses the maturation of miR-154-5p to increase cell invasion and migration

Jihui Zhou,Peng Yang,Haizhou Huang,Li Xu,Shibang Lin

doi:10.1186/s13018-021-02809-4

Abstract

BackgroundCirc-ATAD1 plays an oncogenic role in gastric cancer. However, its roles in other cancers are unclear. We aimed to analyze the role of circ-ATAD1 in osteosarcoma (OS).MethodsThe expression levels of circ-ATAD1, mature miR-154-5p, and premature miR-154-5p in paired OS and non-tumor tissues from 56 OS patients were determined using RT-qPCR. Nuclear fractionation assay was performed to analyze the subcellular location of circ-ATAD1. The interaction between circ-ATAD1 and premature miR-154-5p was analyzed using RNA pull-down assay. The role of circ-ATAD1 in regulating miR-154-5p maturation was analyzed using RT-qPCR in cells with overexpression. Transwell assays were performed to analyze the roles of circ-ATAD1 and miR-154-5p in regulating OS cell invasion and migration.ResultsCirc-ATAD1 was overexpressed in OS compared to non-tumor tissues and was detected in the nuclei of OS cells. Mature miR-154-5p, but not premature miR-154-5p, was downregulated in OS tissues compared to non-tumor tissues and was inversely correlated with circ-ATAD1. In OS cells, circ-ATAD1 overexpression decreased the expression of mature miR-154-5p, but not premature miR-154-5p. Transwell assay analysis showed that circ-ATAD1 overexpression increased cell invasion and migration, and mature miR-154-5p overexpression suppressed these cell behaviors. In addition, circ-ATAD1 overexpression reduced the effects of mature miR-154-5p overexpression on cell behaviors.ConclusionsCirc-ATAD1 is overexpressed in OS and suppresses miR-154-5p maturation to increase cell invasion and migration.

Highlights

Osteosarcoma (OS), refers to osteogenic sarcoma, is the most common type of bone malignancies [1]
Levels of circ‐ATAD1 and mature miR‐154‐5p, but not premature miR‐154‐5p, were altered in OS The levels of circ-ATAD1, mature miR-154-5p, and premature miR-154-5p in paired OS and non-tumor tissues from 56 OS patients were determined by RT-qPCR
Circ-ATAD1 is overexpressed (Fig. 1A, p < 0.01), while mature miR-154-5p was under-expressed in OS tissues (Fig. 1B, p < 0.01) than in non-tumor tissues

Summary

Introduction

Osteosarcoma (OS), refers to osteogenic sarcoma, is the most common type of bone malignancies [1]. With the advantages of fewer adverse effects and high efficiency, molecular targeted therapy, which can be applied to regulate cancer-related gene expression, has shown potentials in the treatment of cancers, including OS [7,8,9,10]. Circular RNAs (circRNAs) have no or limited coding capacity, but they affect cancer development mainly by regulating the expression of protein-coding genes [11, 12], suggesting that circRNAs are potential targets for cancer therapy. Circ-ATAD1 has been reported to play an oncogenic role in gastric cancer [13]. We analyzed the interaction between circ-ATAD1 and miR-154-5p in OS. Circ-ATAD1 plays an oncogenic role in gastric cancer. We aimed to analyze the role of circ-ATAD1 in osteosarcoma (OS)

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