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微小RNA-139靶向纤连蛋白1以抑制甲状腺乳头状癌进展。

MicroRNA-139 targets fibronectin 1 to inhibit papillary thyroid carcinoma progression.

作者信息

Ye Ying, Zhuang Juhua, Wang Guoyu, He Saifei, Ni Jing, Xia Wei

机构信息

Department of Nuclear Medicine, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):7799-7806. doi: 10.3892/ol.2017.7201. Epub 2017 Oct 17.

Abstract

Thyroid cancer is the most common tumour of the endocrine system, and its incidence rate has markedly increased over the past several decades. Aberrantly expressed microRNAs (miRNAs) are reportedly involved in the formation and progression of papillary thyroid carcinoma (PTC) by regulating their target genes. Thus, miRNAs may be potential molecular biomarkers for the prediction and prognosis of PTC, and also as novel therapeutic targets for patients with PTC. miR-139 has recently been reported to be aberrantly expressed in several types of cancer. However, the expression levels, biological functions and the associated molecular mechanism of miR-139 in PTC have not been clearly elucidated. The results of the present study revealed that miR-139 expression was downregulated in PTC tissues and cell lines when compared with adjacent normal tissues and normal human thyroid cells, respectively. The restoration of miR-139 expression suppressed cellular proliferation and invasion in PTC . In addition, fibronectin 1 (FN1) was identified as a direct target of miR-139 in PTC. Furthermore, FN1 was highly expressed in PTC tissues and negatively associated with miR-139 expression. Moreover, the tumour-suppressive effects of miR-139 overexpression on PTC cells were ameliorated by ectopic FN1 expression. To the best of our knowledge, the present study is the first to demonstrate that miR-139 may serve as a tumour suppressor and serve important roles in inhibiting tumourigenesis by targeting FN1 in PTC cells.

摘要

甲状腺癌是内分泌系统最常见的肿瘤,在过去几十年中其发病率显著上升。据报道,异常表达的微小RNA(miRNA)通过调节其靶基因参与甲状腺乳头状癌(PTC)的形成和进展。因此,miRNA可能是PTC预测和预后的潜在分子生物标志物,也可作为PTC患者的新型治疗靶点。最近有报道称miR-139在几种类型的癌症中异常表达。然而,miR-139在PTC中的表达水平、生物学功能及相关分子机制尚未明确阐明。本研究结果显示,与相邻正常组织和正常人甲状腺细胞相比,miR-139在PTC组织和细胞系中的表达分别下调。miR-139表达的恢复抑制了PTC中的细胞增殖和侵袭。此外,纤连蛋白1(FN1)被确定为PTC中miR-139的直接靶点。此外,FN1在PTC组织中高表达,且与miR-139表达呈负相关。而且,异位表达FN1可改善miR-139过表达对PTC细胞的肿瘤抑制作用。据我们所知,本研究首次证明miR-139可能作为一种肿瘤抑制因子,通过靶向PTC细胞中的FN1在抑制肿瘤发生中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e6/5727643/e62de7587d9a/ol-14-06-7799-g00.jpg

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