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长链非编码 RNA SCAMP1 通过靶向 miR-137/CXCL12 轴促进卵巢癌细胞侵袭和血管生成。

Long Noncoding RNA SCAMP1 Targets miR-137/CXCL12 Axis to Boost Cell Invasion and Angiogenesis in Ovarian Cancer.

机构信息

Department of Oncology, Xuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Xuzhou, P.R. China.

Nanjing University of Chinese Medicine, Nanjing, P.R. China.

出版信息

DNA Cell Biol. 2020 Jun;39(6):1041-1050. doi: 10.1089/dna.2019.5312. Epub 2020 May 14.

DOI:10.1089/dna.2019.5312
PMID:32401536
Abstract

Ovarian cancer (OC) is one of gynecological malignancies that seriously affects women's health. Mounting evidence demonstrated that long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) play important roles in various biological processes related to the pathogenesis of OC. This research aimed to investigate the regulatory mechanism of lncRNA SCAMP1/miR-137/CXCL12 (C-X-C motif chemokine ligand 12) axis on OC progression. In this study, we found that SCAMP1 was highly expressed in OC cells, which promoted OC cell invasion and angiogenesis. In addition, our research confirmed that SCAMP1 could bind with miR-137, and SCAMP1 sponged miR-137 to accelerate the progression of OC. We also observed that CXCL12 was a downstream target gene for miR-137, and miR-137 targeted CXCL12 to participate in the regulation of OC. Finally, through TCGA database, we found that SCAMP1 (or CXCL12) was upregulated as well as miR-137 was downregulated in OC tissues, and high (or low) level of them was associated with poor prognosis. miR-137 expression was negatively correlated with SCAMP1 (or CXCL12) expression, and SCAMP1 expression was positively correlated with CXCL12 expression in OC. In summary, our study clarified the role of SCAMP1/miR-137/CXCL12 axis in OC, and this finding may provide a potential therapeutic target of OC.

摘要

卵巢癌(OC)是一种严重影响女性健康的妇科恶性肿瘤。越来越多的证据表明,长链非编码 RNA(lncRNA)、微小 RNA(miRNA)和信使 RNA(mRNA)在与 OC 发病机制相关的各种生物学过程中发挥重要作用。本研究旨在探讨 lncRNA SCAMP1/miR-137/CXCL12(C-X-C 基序趋化因子配体 12)轴对 OC 进展的调控机制。在这项研究中,我们发现 SCAMP1 在 OC 细胞中高表达,促进 OC 细胞侵袭和血管生成。此外,我们的研究证实 SCAMP1 可以与 miR-137 结合,SCAMP1 海绵 miR-137 加速 OC 的进展。我们还观察到 CXCL12 是 miR-137 的下游靶基因,miR-137 靶向 CXCL12 参与 OC 的调节。最后,通过 TCGA 数据库,我们发现 OC 组织中 SCAMP1(或 CXCL12)上调以及 miR-137 下调,并且它们的高水平与预后不良相关。miR-137 的表达与 SCAMP1(或 CXCL12)的表达呈负相关,而在 OC 中 SCAMP1 的表达与 CXCL12 的表达呈正相关。总之,我们的研究阐明了 SCAMP1/miR-137/CXCL12 轴在 OC 中的作用,这一发现可能为 OC 提供潜在的治疗靶点。

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