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Hsa_circ_0032463 通过调节 miR-330-3p/PNN 轴在骨肉瘤中起肿瘤促进作用。

Hsa_circ_0032463 acts as the tumor promoter in osteosarcoma by regulating the miR‑330‑3p/PNN axis.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.

出版信息

Int J Mol Med. 2021 May;47(5). doi: 10.3892/ijmm.2021.4925. Epub 2021 Mar 31.

Abstract

Osteosarcoma (OS), also known as bone cancer, is a threat to the lives of millions of adolescents worldwide. Although dedicated efforts have been invested in reducing the mortality rate of this bone cancer, the research community is yet to find the exact causes of OS. Thus, the present research aimed to study the association between circular RNA circ_0032463 and OS progression. The impact of circ_0032463 on cells with OS was first evaluated using reverse transcription‑quantitative PCR. This evaluation was followed by the assessment of cell proliferation, viability, apoptosis, invasion and adhesion using BrdU, Cell Counting Kit‑8, flow cytometry, Transwell and cell adhesion assays, respectively. RNA pull‑down, RNA immunoprecipitation chip and dual‑luciferase reporter systems were utilized to investigate the relationship between circ_0032463, microRNA (miR)‑330‑3p and Pinin desmosome associated protein (PNN) in OS. The findings indicated that circ_0032463 and PNN were highly expressed in OS tissues and OS cell lines, and that they facilitated cell proliferation, viability, invasion and adhesion, but attenuated cell apoptosis in OS cells. The low expression of miR‑330‑3p suppressed OS development. It was also noted that circ_0032463 inhibited miR‑330‑3p to upregulate PNN expression. In conclusion, this study confirmed that by regulating the miR‑330‑3p/PNN axis, circular RNA circ_0032463 could function as a tumor enhancer in cells with OS.

摘要

骨肉瘤(OS),又称骨癌,是全球数以百万计青少年生命的威胁。尽管人们为降低这种骨癌的死亡率做出了巨大努力,但研究界仍未找到 OS 的确切病因。因此,本研究旨在研究环状 RNA circ_0032463 与 OS 进展之间的关系。首先使用逆转录-定量 PCR 评估 circ_0032463 对 OS 细胞的影响。随后,分别使用 BrdU、细胞计数试剂盒-8、流式细胞术、Transwell 和细胞黏附测定法评估细胞增殖、活力、凋亡、侵袭和黏附。利用 RNA 下拉、RNA 免疫沉淀芯片和双荧光素酶报告系统研究 circ_0032463、微小 RNA(miR)-330-3p 和桥粒斑蛋白(PNN)在 OS 中的关系。结果表明,circ_0032463 和 PNN 在 OS 组织和 OS 细胞系中高表达,促进 OS 细胞的增殖、活力、侵袭和黏附,但抑制细胞凋亡。miR-330-3p 的低表达抑制了 OS 的发展。此外,还发现 circ_0032463 抑制 miR-330-3p 以上调 PNN 表达。总之,本研究证实,通过调节 miR-330-3p/PNN 轴,环状 RNA circ_0032463 可作为 OS 细胞中的肿瘤增强子发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ade/8012025/98b4caee032f/IJMM-47-05-04925-g00.jpg

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