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长链非编码RNA前列腺雄激素调节转录本1(PART 1)在骨肉瘤中作为癌基因发挥作用,通过吸附miR-20b-5p上调BAMBI。

LncRNA prostate androgen-regulated transcript 1 (PART 1) functions as an oncogene in osteosarcoma via sponging miR-20b-5p to upregulate BAMBI.

作者信息

Pan Zhimin, Mo Fengbo, Liu Hucheng, Zeng Jin, Huang Kai, Huang Sheng, Cao Zhiyou, Xu Xiaoyu, Xu Jianyun, Liu Tianmi, Huang Jiang

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Department of Orthopedics, Zhabei Central Hospital of Jing'an District, Shanghai, China.

出版信息

Ann Transl Med. 2021 Mar;9(6):488. doi: 10.21037/atm-21-658.

Abstract

BACKGROUND

Osteosarcoma (OS) is an aggressive bone cancer that most commonly affects adolescents and children. Emerging studies have shown that long noncoding RNA (lncRNA) performs essential roles in the occurrence and development of many tumors. Prostate androgen-regulated transcript 1 (PART 1) has been reported as a tumor oncogene; despite this, the mechanisms underlying its involvement in OS are unclear.

METHODS

OS and paired normal tissue samples were obtained, and gene expressions were detected by real time-quantitative polymerase chain reaction (RT-qPCR). The functions of PART 1 in OS cell proliferation, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8) and Transwell assays. Furthermore, the binding sites of PART 1 and miR-20b-5p as well as those between miR-20b-5p and bone morphogenic protein and activin membrane-bound inhibitor homolog (BAMBI) were verified by bioinformatics analysis and dual-luciferase reporter assay.

RESULTS

Our study found obvious overexpression of PART 1 in OS tissues and cells. Furthermore, PART 1 overexpression facilitated OS cell proliferation, invasion, and migration. Further mechanistic investigations revealed that PART 1 could sponge to miR-20b-5p, which was expressed at a low level in OS tissues and cells. Importantly, miR-20b-5p overexpression inhibited OS cell proliferation, invasion, and migration. Additionally, BAMBI was confirmed as a downstream gene of miR-20b-5p, and its expression was reversely modulated by miR-20b-5p and positively modulated by PART 1. Rescue experiments suggested that BAMBI was involved in PART 1-mediated promotion of OS progression.

CONCLUSIONS

PART 1 serves as a competing endogenous RNA to promote OS tumorigenesis via its regulation of the miR-20b-5p/BAMBI axis, which may provide a promising therapeutic biomarkers for OS patients.

摘要

背景

骨肉瘤(OS)是一种侵袭性骨癌,最常影响青少年和儿童。新兴研究表明,长链非编码RNA(lncRNA)在许多肿瘤的发生和发展中发挥着重要作用。前列腺雄激素调节转录本1(PART 1)已被报道为一种肿瘤癌基因;尽管如此,其参与骨肉瘤的潜在机制尚不清楚。

方法

获取骨肉瘤及配对的正常组织样本,通过实时定量聚合酶链反应(RT-qPCR)检测基因表达。采用细胞计数试剂盒-8(CCK-8)和Transwell实验确定PART 1在骨肉瘤细胞增殖、侵袭和迁移中的作用。此外,通过生物信息学分析和双荧光素酶报告基因实验验证PART 1与miR-20b-5p以及miR-20b-5p与骨形态发生蛋白和激活素膜结合抑制剂同源物(BAMBI)之间的结合位点。

结果

我们的研究发现PART 1在骨肉瘤组织和细胞中明显过表达。此外,PART 1过表达促进了骨肉瘤细胞的增殖、侵袭和迁移。进一步的机制研究表明,PART 1可以吸附miR-20b-5p,而miR-20b-5p在骨肉瘤组织和细胞中表达水平较低。重要的是,miR-20b-5p过表达抑制了骨肉瘤细胞的增殖、侵袭和迁移。此外,BAMBI被确认为miR-20b-5p的下游基因,其表达受到miR-20b-5p的反向调节和PART 1的正向调节。挽救实验表明,BAMBI参与了PART 1介导的骨肉瘤进展促进过程。

结论

PART 1作为一种竞争性内源性RNA,通过调节miR-20b-5p/BAMBI轴促进骨肉瘤的发生,这可能为骨肉瘤患者提供一种有前景的治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/262f/8039658/ed7d2057caf8/atm-09-06-488-f1.jpg

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