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LINK-A长链非编码RNA通过上调缺氧诱导因子1α(HIF1α)在骨肉瘤转移中发挥作用。

LINK-A lncRNA functions in the metastasis of osteosarcoma by upregulating HIF1α.

作者信息

Zhao Boming, Liu Kebin, Cai Lin

机构信息

Department of Orthopaedic Surgery, Zhongnan Hospital Affiliated to Medical College of Wuhan University, Wuhan, Hubei 430071, P.R. China.

Department of Orthopaedic Surgery, First People's Hospital of Jingzhou, Jingzhou, Hubei 434000, P.R. China.

出版信息

Oncol Lett. 2019 Jun;17(6):5005-5011. doi: 10.3892/ol.2019.10177. Epub 2019 Mar 21.

Abstract

Long intergenic non-coding RNA for kinase activation (LINK-A) long non-coding RNA (lncRNA) is an oncogenic lncRNA in triple-negative breast cancer. The involvement of LINK-A lncRNA in other diseases is unknown. The present study aimed to investigate the possible involvement of LINK-A lncRNA in osteosarcoma. The results demonstrated that plasma levels of LINK-A lncRNA were significantly higher in patients with metastatic osteosarcoma (MO) compared with healthy controls and patients with non-metastatic osteosarcoma (NMO). LINK-A lncRNA overexpression significantly promoted cancer cell migration and invasion in osteosarcoma cell lines MG-63 and U20S. Upregulated expression of hypoxia-inducible factor 1α (HIF1α) was observed in cancer cells following LINK-A lncRNA overexpression. Exogenous HIF1α treatment did not significantly affect the expression of LINK-A lncRNA in cancer cells, whereas treatment with an HIF1α inhibitor significantly attenuated the effects of LINK-A lncRNA overexpression on cancer cell migration and invasion. Based on the results it was concluded that LINK-A lncRNA participated in the metastasis of osteosarcoma by upregulating HIF1α; upregulation of LINK-A lncRNA may serve as a potential diagnostic biomarker for patients with MO but not in those with NMO.

摘要

激酶激活长链基因间非编码RNA(LINK-A)长链非编码RNA(lncRNA)是三阴性乳腺癌中的一种致癌lncRNA。LINK-A lncRNA在其他疾病中的作用尚不清楚。本研究旨在探讨LINK-A lncRNA在骨肉瘤中的可能作用。结果表明,与健康对照和非转移性骨肉瘤(NMO)患者相比,转移性骨肉瘤(MO)患者血浆中LINK-A lncRNA水平显著升高。LINK-A lncRNA过表达显著促进骨肉瘤细胞系MG-63和U20S中的癌细胞迁移和侵袭。LINK-A lncRNA过表达后,癌细胞中缺氧诱导因子1α(HIF1α)的表达上调。外源性HIF1α处理对癌细胞中LINK-A lncRNA的表达无显著影响,而用HIF1α抑制剂处理可显著减弱LINK-A lncRNA过表达对癌细胞迁移和侵袭的影响。基于这些结果得出结论,LINK-A lncRNA通过上调HIF1α参与骨肉瘤转移;LINK-A lncRNA的上调可能作为MO患者而非NMO患者的潜在诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a493/6507337/3771ae46172b/ol-17-06-5005-g00.jpg

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