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YY1 上调的 TNK2-AS1 通过靶向 miR-4319/WDR1 促进骨肉瘤的发生发展。

TNK2-AS1 upregulated by YY1 boosts the course of osteosarcoma through targeting miR-4319/WDR1.

机构信息

Department of Bone and Soft Tumor, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

出版信息

Cancer Sci. 2021 Feb;112(2):893-905. doi: 10.1111/cas.14727. Epub 2020 Dec 1.

Abstract

Mounting research papers have suggested that long non-coding RNAs (lncRNAs) elicit important functions in the progression of osteosarcoma (OS). This study focused on the role of TNK2-AS1 in OS. TNK2-AS1 was powerfully expressed in OS tissues and cell lines. In addition, TNK2-AS1 downregulation inhibited proliferative, migratory, and invasive capacities while promoting apoptosis in OS cells. miR-4319 was removed by TNK2-AS1 and therefore TNK2-AS1 elevated WDR1 expression in OS cells. miR-4319 had an inhibitory influence on OS progression, while WDR1 was a contributor to OS progression. Rescue assays certified that TNK2-AS1 promoted malignant phenotypes in vitro and the growth in vivo of OS cells by upregulating WDR1. In depth, we found that YY1 accelerated the transcription of TNK2-AS1 in OS cells, and that its role in OS also depended on TNK2-AS1-regulated WDR1. In conclusion, TNK2-AS1 was positively modulated by YY1 and aggravated the development of OS by 'sponging' miR-4319 to elevate WDR1. The findings highlighted that TNK2-AS1 might be a promising target for the treatment of OS.

摘要

越来越多的研究论文表明,长非编码 RNA(lncRNA)在骨肉瘤(OS)的进展中发挥重要作用。本研究重点关注 TNK2-AS1 在 OS 中的作用。TNK2-AS1 在 OS 组织和细胞系中表达水平较高。此外,下调 TNK2-AS1 抑制了 OS 细胞的增殖、迁移和侵袭能力,同时促进了细胞凋亡。TNK2-AS1 通过去除 miR-4319 从而上调 OS 细胞中的 WDR1 表达。miR-4319 对 OS 进展具有抑制作用,而 WDR1 则促进 OS 进展。挽救实验证实,TNK2-AS1 通过上调 WDR1 促进 OS 细胞的体外恶性表型和体内生长。深入研究发现,YY1 在 OS 细胞中加速 TNK2-AS1 的转录,其在 OS 中的作用也依赖于 TNK2-AS1 调节的 WDR1。总之,TNK2-AS1 被 YY1 正向调控,并通过“海绵吸附”miR-4319 来升高 WDR1,从而加重 OS 的发展。这些发现表明,TNK2-AS1 可能成为治疗 OS 的一个有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b52/7893995/870dbdfe89c7/CAS-112-893-g001.jpg

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