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FBLN5 是 microRNA-27a-3p 的靶标,可抑制高级别浆液性卵巢癌的肿瘤发生和进展。

FBLN5 is targeted by microRNA‑27a‑3p and suppresses tumorigenesis and progression in high‑grade serous ovarian carcinoma.

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

出版信息

Oncol Rep. 2020 Nov;44(5):2143-2151. doi: 10.3892/or.2020.7749. Epub 2020 Sep 3.

Abstract

High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological malignancies; however, the precise molecular mechanisms have not been fully characterized. Fibulin‑5 (FBLN‑5) is an extracellular matrix (ECM) glycoprotein, and plays a crucial role in maintaining the stability of ECM structures, regulating cell proliferation and tumorigenesis. In the present study, the expression of FBLN‑5, as determined by western blot analysis and immunohistochemistry, was significantly increased in normal fallopian tube (FT) samples compared with that in HGSOC samples, and decreased FBLN5 expression was associated with unfavorable prognosis of HGSOC. Functional characterization revealed that FBLN5 overexpression significantly inhibited migration, invasion and proliferation abilities of ovarian cancer cells in vitro. Furthermore, micro (mi)RNA‑27a‑3p (miR‑27a‑3p) was revealed to be increased in HGSOC, and dual‑luciferase reporter assay indicated that miR‑27a‑3p was functioned as a negative regulator of FBLN5 by directly binding with its 3'‑untranslated region. Collectively, FBLN5 expression was associated with prognosis, proliferation, and metastasis in HGSOC. We hypothesized that FBLN5 was targeted by miR‑27a‑3p and may serve as a biomarker and provide a new therapeutic approach for the treatment of HGSOC.

摘要

高级别浆液性卵巢癌(HGSOC)是最致命的妇科恶性肿瘤之一;然而,其确切的分子机制尚未完全阐明。纤连蛋白 5(FBLN-5)是细胞外基质(ECM)糖蛋白的一种,在维持 ECM 结构稳定性、调节细胞增殖和肿瘤发生方面发挥着关键作用。在本研究中,通过 Western blot 分析和免疫组织化学检测,FBLN-5 的表达在正常输卵管(FT)样本中明显高于 HGSOC 样本,并且 FBLN5 表达降低与 HGSOC 的不良预后相关。功能特征分析表明,FBLN5 过表达可显著抑制卵巢癌细胞在体外的迁移、侵袭和增殖能力。此外,miRNA-27a-3p(miR-27a-3p)在 HGSOC 中表达增加,双荧光素酶报告基因实验表明 miR-27a-3p 通过直接与其 3'非翻译区结合,作为 FBLN5 的负调节剂。总之,FBLN5 的表达与 HGSOC 的预后、增殖和转移有关。我们假设 FBLN5 是由 miR-27a-3p 靶向的,可能作为生物标志物,并为 HGSOC 的治疗提供新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/258b/7550983/87d13c9c3c6c/OR-44-05-2143-g00.jpg

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