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miR-557 通过降低 HOXB9 并使 EMT 过程失活来抑制骨肉瘤细胞的恶性行为。

miR-557 suppressed the malignant behaviours of osteosarcoma cells by reducing HOXB9 and deactivating the EMT process.

机构信息

Department of Spinal Orthopedics, Weihai Municipal Hospital, Weihai City, P. R. China.

Department of Joint and Sports Medicine, Shandong Provincial Third Hospital affiliated to Shandong University, Jinan City, Shandong Province, P. R. China.

出版信息

Artif Cells Nanomed Biotechnol. 2021 Dec;49(1):230-239. doi: 10.1080/21691401.2021.1890100.

DOI:10.1080/21691401.2021.1890100
PMID:33666541
Abstract

MicroRNAs (miRNAs) are vital gene regulators, which play a profound role in the process of forming and developing many diseases, especially tumour. The study intends to excavate the potential regulatory mechanisms of miR-557 and its targeting gene Homeobox B9 (HOXB9) in osteosarcoma. GEO dataset on osteosarcoma was applied to detect the expression of miR-557 and HOXB9. Associations between miR-557 and HOXB9 were speculated by prediction software and verified by dual luciferase assay. Cell proliferation, colony formation and mobility were measured by cell counting kit-8, plate clone formation and transwell assays. Expression of mesenchymal transitions (MTs) related proteins was assessed by western blot analysis. Low expression of miR-557 was presented in osteosarcoma tissues and cell lines. Upregulation of miR-557 restrained osteosarcoma cells proliferation, movement and MT process. HOXB9, served as a target gene of miR-557, was highly expressed in osteosarcoma, and its high expression was associated with poor prognosis in patients with osteosarcoma. In addition, overexpression of HOXB9 attenuated the inhibitory effects of miR-557 on tumour progression by MT process. Overexpression of miR-557 suppressed the growth, metastasis and MT process of osteosarcoma cells by targeting HOXB9, affording novel molecular selection for targeted therapy of osteosarcoma.

摘要

微小 RNA(miRNA)是重要的基因调控因子,在许多疾病的发生和发展过程中发挥着重要作用,尤其是肿瘤。本研究旨在挖掘 miR-557 及其靶基因 Homeobox B9(HOXB9)在骨肉瘤中的潜在调控机制。应用 GEO 骨肉瘤数据集检测 miR-557 和 HOXB9 的表达。通过预测软件推测 miR-557 和 HOXB9 之间的关联,并通过双荧光素酶报告基因实验验证。通过细胞计数试剂盒-8、平板克隆形成和 Transwell 实验检测细胞增殖、集落形成和迁移。通过 Western blot 分析评估间充质转化(MTs)相关蛋白的表达。骨肉瘤组织和细胞系中 miR-557 表达降低。miR-557 的上调抑制骨肉瘤细胞的增殖、迁移和 MT 过程。HOXB9 作为 miR-557 的靶基因,在骨肉瘤中高表达,其高表达与骨肉瘤患者的预后不良相关。此外,HOXB9 的过表达通过 MT 过程减弱了 miR-557 对肿瘤进展的抑制作用。miR-557 通过靶向 HOXB9 抑制骨肉瘤细胞的生长、转移和 MT 过程,为骨肉瘤的靶向治疗提供了新的分子选择。

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