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正反馈环 SP1/MIR17HG/miR-130a-3p 促进骨肉瘤增殖和顺铂耐药性。

Positive feedback loop SP1/MIR17HG/miR-130a-3p promotes osteosarcoma proliferation and cisplatin resistance.

机构信息

Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiao Tong University, Xian, Shaanxi, 710000, China.

Department of Orthopaedic, Hong Hui Hospital, Xi'an Jiao Tong University, Xian, Shaanxi, 710000, China.

出版信息

Biochem Biophys Res Commun. 2020 Jan 15;521(3):739-745. doi: 10.1016/j.bbrc.2019.10.180. Epub 2019 Nov 6.

DOI:10.1016/j.bbrc.2019.10.180
PMID:31706574
Abstract

Long noncoding RNAs (lncRNAs) have been identified to be critical regulator in the osteosarcoma (OS) tumorigenesis. However, the role of lncRNA MIR17HG in the OS proliferation and chemotherapy resistance is still unclear. Here, this research aims to investigate the function of lncRNA MIR17HG in the OS proliferation and cisplatin resistance. Clinically, results revealed that higher MIR17HG expression was associated with shorter overall survival. Functional investigations indicated that MIR17HG promoted the proliferation, invasion and cisplatin resistance of OS cells in vitro, and the MIR17HG knockdown inhibited the growth in vivo. Mechanistically, MIR17HG targeted the miR-130a-3p/SP1 axis, moreover, transcription factor SP1 bind with the MIR17HG promoter region to promote its expression. Taken together, MIR17HG displays the tumor-promotive role in the progression of OS through SP1/MIR17HG/miR-130a-3p/SP1 feedback loop. Our findings might help us to offer novel therapeutic strategies for OS.

摘要

长链非编码 RNA(lncRNA)已被鉴定为骨肉瘤(OS)肿瘤发生的关键调节剂。然而,lncRNA MIR17HG 在 OS 增殖和化疗耐药中的作用仍不清楚。本研究旨在探讨 lncRNA MIR17HG 在 OS 增殖和顺铂耐药中的作用。临床上,结果表明 MIR17HG 表达水平较高与总生存期较短有关。功能研究表明,MIR17HG 在体外促进 OS 细胞的增殖、侵袭和顺铂耐药,而 MIR17HG 敲低则抑制体内生长。机制上,MIR17HG 靶向 miR-130a-3p/SP1 轴,此外,转录因子 SP1 与 MIR17HG 启动子区域结合以促进其表达。总之,MIR17HG 通过 SP1/MIR17HG/miR-130a-3p/SP1 反馈环在 OS 的进展中发挥促肿瘤作用。我们的研究结果可能为 OS 提供新的治疗策略。

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