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TUSC8 通过海绵吸附 miR-197-3p 和靶向 EHD2 抑制骨肉瘤的发展。

TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2.

机构信息

Department of Orthopaedics, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.

Department of Spine Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.

出版信息

Int J Mol Med. 2020 Oct;46(4):1311-1320. doi: 10.3892/ijmm.2020.4684. Epub 2020 Jul 27.

DOI:10.3892/ijmm.2020.4684
PMID:32945345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7447318/
Abstract

Osteosarcoma (OS) is one of the most common malignant bone tumours and generally occurs in children and adolescents. Increasing evidence has demonstrated that dysregulated long non‑coding RNAs (lncRNAs) play crucial roles in the progression of various human neoplasms. Among these, tumour suppressor candidate 8 (TUSC8) is a novel lncRNA and has been reported to function as a tumour suppressor in cervical cancer. However, the exact role of TUSC8 in OS remains largely unknown. In the present study, it was observed that TUSC8 was markedly downregulated in OS tissues and cell lines. Functional experiments demonstrated that the overexpression of TUSC8 significantly suppressed the proliferation, migration, invasion and epithelial‑mesenchymal transition (EMT), whereas it accelerated the apoptosis of OS cells. Mechanistically, TUSC8 served as a sponge for miR‑197‑3p, and EH‑domain containing 2 (EHD2) was identified as a downstream target molecule of miR‑197‑3p. Further investigations indicated that EHD2 knockdown significantly reversed the effects on OS cellular processes induced by TUSC8 overexpression. On the whole, these findings indicate that TUSC8 functions as a competing endogenous RNA (ceRNA) to suppress OS cell growth and EMT via the miR‑197‑3p/EHD2 axis. TUSC8 may thus function as a potential therapeutic target in OS treatment.

摘要

骨肉瘤(OS)是最常见的恶性骨肿瘤之一,通常发生在儿童和青少年中。越来越多的证据表明,失调的长非编码 RNA(lncRNA)在各种人类肿瘤的进展中发挥着关键作用。在这些 lncRNA 中,肿瘤抑制候选基因 8(TUSC8)是一种新型的 lncRNA,据报道其在宫颈癌中发挥肿瘤抑制作用。然而,TUSC8 在 OS 中的确切作用仍知之甚少。在本研究中,观察到 TUSC8 在 OS 组织和细胞系中明显下调。功能实验表明,TUSC8 的过表达显著抑制了 OS 细胞的增殖、迁移、侵袭和上皮间质转化(EMT),而促进了 OS 细胞的凋亡。机制上,TUSC8 作为 miR-197-3p 的海绵,EH 结构域包含 2(EHD2)被鉴定为 miR-197-3p 的下游靶分子。进一步的研究表明,EHD2 的敲低显著逆转了 TUSC8 过表达对 OS 细胞过程的影响。总的来说,这些发现表明,TUSC8 通过 miR-197-3p/EHD2 轴作为竞争内源性 RNA(ceRNA)抑制 OS 细胞生长和 EMT。因此,TUSC8 可能成为 OS 治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/1c3b463d8fd2/IJMM-46-04-1311-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/3ee551bfddae/IJMM-46-04-1311-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/b76f0589883f/IJMM-46-04-1311-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/2119ca3a48c8/IJMM-46-04-1311-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/3f64560560bc/IJMM-46-04-1311-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/1c3b463d8fd2/IJMM-46-04-1311-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/3ee551bfddae/IJMM-46-04-1311-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/b76f0589883f/IJMM-46-04-1311-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/2119ca3a48c8/IJMM-46-04-1311-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/3f64560560bc/IJMM-46-04-1311-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9692/7447318/1c3b463d8fd2/IJMM-46-04-1311-g04.jpg

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