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长链非编码 RNA TP73-AS1 的敲低通过靶向 miR-490-3p/TWIST1 轴抑制三阴性乳腺癌细胞血管生成拟态。

Knockdown of long non-coding RNA TP73-AS1 suppresses triple negative breast cancer cell vasculogenic mimicry by targeting miR-490-3p/TWIST1 axis.

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.

Department of Ultrasonography, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China.

出版信息

Biochem Biophys Res Commun. 2018 Oct 12;504(4):629-634. doi: 10.1016/j.bbrc.2018.08.122. Epub 2018 Sep 5.

Abstract

Triple negative breast cancer (TNBC) is among the most clinically aggressive subtypes of breast cancer. Despite the availability of new drugs, patients suffering TNBC bear disheartening prognosis. Vasculogenic mimicry (VM) is a malignant tumor specific non-endothelial vascular network, which provide oxygen and nutrients to tumor cells and facilitate tumor progression. Therefore targeting TNBC VM formation may contribute to tumor treatment. In this study, we found that long non-coding RNA TP73 antisense RNA 1 (TP73-AS1) was upregulated in VM positive TNBC tissues. Knockdown of TP73-AS1 suppressed TNBC cell line MDA-MB-231 cell VM formation in vitro. In addition, RNA immunoprecipitation assay and dual luciferase reporter assay showed that TP73-AS1 bound to miR-490-3p in a sequence-specific manner. miR-490-3p was downregulated in VM positive tissues and was involved in TP73-AS1-mediated MDA-MB-231 cell VM formation. Furthermore, TWIST1 was a target of miR-490-3p and participated in TP73-AS1/miR-490-3p-modulated MDA-MB-231 cell VM formation. Findings in this study may provide insight in TNBC management.

摘要

三阴性乳腺癌(TNBC)是乳腺癌中最具侵袭性的亚型之一。尽管有新的药物可用,但患有 TNBC 的患者预后令人沮丧。血管生成拟态(VM)是一种恶性肿瘤特异性的非内皮血管网络,为肿瘤细胞提供氧气和营养物质,并促进肿瘤进展。因此,靶向 TNBC VM 形成可能有助于肿瘤治疗。在这项研究中,我们发现长非编码 RNA TP73 反义 RNA 1(TP73-AS1)在 VM 阳性 TNBC 组织中上调。TP73-AS1 的敲低抑制了体外 TNBC 细胞系 MDA-MB-231 细胞的 VM 形成。此外,RNA 免疫沉淀测定和双荧光素酶报告基因测定表明,TP73-AS1 以序列特异性方式结合 miR-490-3p。VM 阳性组织中 miR-490-3p 下调,并参与 TP73-AS1 介导的 MDA-MB-231 细胞 VM 形成。此外,TWIST1 是 miR-490-3p 的靶基因,并参与 TP73-AS1/miR-490-3p 调节的 MDA-MB-231 细胞 VM 形成。本研究的结果可能为 TNBC 的治疗提供新的思路。

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