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长链非编码 RNA ADAMTS9-AS2 通过靶向 miR-182-5p/FOXF2 信号通路调控卵巢癌进展。

LncRNA ADAMTS9-AS2 regulates ovarian cancer progression by targeting miR-182-5p/FOXF2 signaling pathway.

机构信息

Department of Gynecologic Oncology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Department of Gastrointestinal Tumor Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471000, Henan Province, China.

出版信息

Int J Biol Macromol. 2018 Dec;120(Pt B):1705-1713. doi: 10.1016/j.ijbiomac.2018.09.179. Epub 2018 Sep 27.

Abstract

Increasing studies revealed that aberrant expression of long non-coding RNAs (lncRNAs) play critical roles in ovarian cancer (OC) progression. However, the roles and underlying mechanisms of ADAMTS9-AS2 in OC remain unclear. In the present study, we showed that ADAMTS9-AS2 expression was significantly decreased in OC tissues and cell lines. Low ADAMTS9-AS2 expression was correlated with advanced FIGO stage, lymph-node metastasis, and poor overall survival of OC patients. Function assays showed that ADAMTS9-AS2 reduced OC cells proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes in vitro and restrained tumor growth in vivo. The underlying mechanism studies indicated that ADAMTS9-AS2 functioned as a competing endogenous RNA (ceRNA) for miR-182-5p to promote cell proliferation and invasion. In addition, we revealed that FOXF2 acted as a direct target of miR-182-5p and mediated the effects of ADAMTS9-AS2 on OC cells progression. Taken together, our data suggested that lncRNA ADAMTS9-AS2 decreased OC progression by regulating miR-182-5p/FOXF2 axis, indicating ADAMTS9-AS2 could serve as a potential therapeutic target for OC treatment.

摘要

越来越多的研究表明,长链非编码 RNA(lncRNAs)的异常表达在卵巢癌(OC)的进展中起着关键作用。然而,ADAMTS9-AS2 在 OC 中的作用和潜在机制仍不清楚。在本研究中,我们表明 ADAMTS9-AS2 的表达在 OC 组织和细胞系中显著降低。低表达 ADAMTS9-AS2 与 OC 患者的FIGO 晚期分期、淋巴结转移和不良总生存期相关。功能测定表明 ADAMTS9-AS2 可降低 OC 细胞的增殖、侵袭和上皮-间充质转化(EMT)过程,并在体内抑制肿瘤生长。潜在机制研究表明,ADAMTS9-AS2 作为 miR-182-5p 的竞争性内源性 RNA(ceRNA),促进细胞增殖和侵袭。此外,我们揭示了 FOXF2 是 miR-182-5p 的直接靶基因,并介导 ADAMTS9-AS2 对 OC 细胞进展的影响。总之,我们的数据表明 lncRNA ADAMTS9-AS2 通过调节 miR-182-5p/FOXF2 轴降低 OC 的进展,表明 ADAMTS9-AS2 可作为 OC 治疗的潜在治疗靶点。

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