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环状 ATAD1 在骨肉瘤(OS)中过表达,抑制 miR-154-5p 的成熟,从而增加细胞侵袭和迁移。

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

机构信息

Department of Traumatic Orthopedics, Maoming People's Hospital, No. 101 Weimin Road, Maoming City, 525000, Guangdong Province, People's Republic of China.

The 9th Recuperation Department of Qingdao Special Servicemen Recuperation Center of PLA NAVY, Qingdao City, 266071, Shandong Province, People's Republic of China.

出版信息

J Orthop Surg Res. 2021 Dec 2;16(1):699. doi: 10.1186/s13018-021-02809-4.

Abstract

BACKGROUND

Circ-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).

METHODS

The 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.

RESULTS

Circ-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.

CONCLUSIONS

Circ-ATAD1 is overexpressed in OS and suppresses miR-154-5p maturation to increase cell invasion and migration.

摘要

背景

Circ-ATAD1 在胃癌中发挥致癌作用。然而,其在其他癌症中的作用尚不清楚。我们旨在分析 Circ-ATAD1 在骨肉瘤(OS)中的作用。

方法

使用 RT-qPCR 测定 56 例 OS 患者配对的 OS 和非肿瘤组织中 Circ-ATAD1、成熟 miR-154-5p 和前体 miR-154-5p 的表达水平。通过核分离测定分析 Circ-ATAD1 的亚细胞定位。使用 RNA 下拉测定分析 Circ-ATAD1 与前体 miR-154-5p 的相互作用。通过在过表达细胞中进行 RT-qPCR 分析 Circ-ATAD1 调节 miR-154-5p 成熟的作用。通过 Transwell 测定分析 Circ-ATAD1 和 miR-154-5p 在调节 OS 细胞侵袭和迁移中的作用。

结果

与非肿瘤组织相比,Circ-ATAD1 在 OS 中表达上调,并在 OS 细胞的核中检测到。与非肿瘤组织相比,OS 组织中成熟 miR-154-5p 下调,而前体 miR-154-5p 上调,且与 Circ-ATAD1 呈负相关。在 OS 细胞中,Circ-ATAD1 过表达降低成熟 miR-154-5p 的表达,但不降低前体 miR-154-5p 的表达。Transwell 分析表明,Circ-ATAD1 过表达增加细胞侵袭和迁移,而过表达成熟 miR-154-5p 抑制这些细胞行为。此外,Circ-ATAD1 过表达降低了成熟 miR-154-5p 过表达对细胞行为的影响。

结论

Circ-ATAD1 在 OS 中过表达,抑制 miR-154-5p 成熟,增加细胞侵袭和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c40/8638470/ebe62500d033/13018_2021_2809_Fig1_HTML.jpg

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