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长链非编码 RNA OIP5-AS1 通过调控 miR-137-3p/PTN 轴介导骨肉瘤对多柔比星的耐药性。

Long noncoding RNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma.

机构信息

Department of Oncology, Sixth People's Hospital East Campus Affiliated to Shanghai Jiao Tong University, Shanghai 201306, China; Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital East Campus, Shanghai 201306, China.

Department of Oncology, Sixth People's Hospital East Campus Affiliated to Shanghai Jiao Tong University, Shanghai 201306, China; Shanghai University of Medicine & Health Sciences Affiliated Sixth People's Hospital East Campus, Shanghai 201306, China.

出版信息

Biomed Pharmacother. 2020 Aug;128:110201. doi: 10.1016/j.biopha.2020.110201. Epub 2020 May 24.

Abstract

Opa-interacting protein 5 antisense RNA1 (OIP5-AS1) has been demonstrated to facilitate proliferation, metastasis and resistance to treatments in various types of cancers. Nevertheless, the exact mechanisms underlying the roles of OIP5-AS1 in osteosarcoma(OS) drug resistance have not yet been clearly elucidated. Therefore, we sought to investigate the functional involvement of OIP5-AS1 in osteosarcoma. Our results indicated that OIP5-AS1 was dramatically up-regulated in osteosarcoma drug-resistant tissues and cells in comparison with drug-sensitive tissues and cells. Also, the knockdown of OIP5-AS1 was found to have decreased doxorubicin resistance of OS cells. Further analyses revealed that OIP5-AS1 operated as a competitor for endogenous RNA of miR-137-3p as well as regulated pleiotrophin(PTN) expression, which has been reported to be an oncogene in OS in previous research. Furthermore, the loss of miR-137-3p or alternatively, the gain of PTN, both resulted in the abolishment of the inhibitory role of OIP5-AS1 silencing the proliferative activity. Our analyses indicated and helped to determine the role of OIP5-AS1 in contributing to tumorigenesis of osteosarcoma via the miR-137-3p/PTN axis and, therefore outlining its potential for use as a therapeutic target against this cancer.

摘要

Opa 相互作用蛋白 5 反义 RNA1(OIP5-AS1)已被证明可促进多种类型癌症的增殖、转移和耐药性。然而,OIP5-AS1 在骨肉瘤(OS)耐药性中的作用的确切机制尚未阐明。因此,我们试图研究 OIP5-AS1 在骨肉瘤中的功能作用。

我们的研究结果表明,与敏感组织和细胞相比,骨肉瘤耐药组织和细胞中 OIP5-AS1 显著上调。此外,OIP5-AS1 的敲低降低了 OS 细胞对阿霉素的耐药性。进一步的分析表明,OIP5-AS1 作为 miR-137-3p 的内源性 RNA 的竞争物起作用,并调节多效蛋白(PTN)的表达,在之前的研究中已报道 PTN 是 OS 的致癌基因。此外,miR-137-3p 的缺失或 PTN 的获得,都导致 OIP5-AS1 沉默增殖活性的抑制作用丧失。

我们的分析表明并有助于确定 OIP5-AS1 通过 miR-137-3p/PTN 轴在促进骨肉瘤发生中的作用,因此概述了其作为针对这种癌症的治疗靶点的潜力。

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