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微小RNA-140-5p通过靶向WNT/β-连环蛋白信号通路中的WNT1抑制胃癌细胞的增殖和侵袭。

MicroRNA-140-5p suppresses cell proliferation and invasion in gastric cancer by targeting WNT1 in the WNT/β-catenin signaling pathway.

作者信息

Cha Yinlian, He Ying, Ouyang Kaobin, Xiong Hailin, Li Jun, Yuan Xia

机构信息

Department of Medical Oncology, Huizhou Municipal Central Hospital of Guangdong Province, Huizhou, Guangdong 516000, P.R. China.

出版信息

Oncol Lett. 2018 Nov;16(5):6369-6376. doi: 10.3892/ol.2018.9480. Epub 2018 Sep 21.

Abstract

MicroRNAs have been suggested as potential regulators in gastric cancer (GC) development through affecting the expression of their target genes. Previous studies have demonstrated that miR-140-5p is downregulated in GC. However, the underlying functional role of miR-140-5p in GC remains largely unknown. The present study revealed that miR-140-5p expression was significantly decreased in 60 GC tissues, compared with corresponding adjacent non-tumor tissues. A lower miR-140-5p expression was significantly associated with lymph node metastasis and an advanced Tumor-Node-Metastasis stage in patients with GC. Furthermore, patients with a lower miR-140-5p expression exhibited shorter disease-free survival and overall survival times. Gain- and loss-of-function assays revealed that increased miR-140-5p expression significantly inhibited GC cell proliferation and invasion ability, as well as the Wnt/β-catenin signaling pathway by decreasing WNT1 and β-catenin expression. However, decreasing miR-140-5p expression had the opposite effects. Bioinformatics methods and dual-luciferase reporter assays revealed that WNT1 was a direct target of miR-140-5p. miR-140-5p suppressed cell proliferation and invasion by regulating WNT1 expression. Therefore, the results of the present study demonstrated that miR-140-5p may serve as a potential prognostic marker and therapeutic target in patients with GC.

摘要

微小RNA已被认为是通过影响其靶基因的表达来调控胃癌(GC)发生发展的潜在因子。先前的研究表明,miR-140-5p在GC中表达下调。然而,miR-140-5p在GC中的潜在功能作用仍不清楚。本研究发现,与相应的癌旁非肿瘤组织相比,60例GC组织中miR-140-5p的表达显著降低。GC患者中较低的miR-140-5p表达与淋巴结转移及较高的肿瘤-淋巴结-转移分期显著相关。此外,miR-140-5p表达较低的患者无病生存期和总生存期较短。功能获得和缺失实验表明,miR-140-5p表达增加显著抑制GC细胞增殖和侵袭能力,以及通过降低WNT1和β-连环蛋白的表达来抑制Wnt/β-连环蛋白信号通路。然而,降低miR-140-5p表达则产生相反的效果。生物信息学方法和双荧光素酶报告基因实验表明,WNT1是miR-140-5p的直接靶点。miR-140-5p通过调节WNT1表达抑制细胞增殖和侵袭。因此,本研究结果表明,miR-140-5p可能是GC患者潜在的预后标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8541/6202481/b8ad8ad9ba3b/ol-16-05-6369-g00.jpg

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