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微小 RNA-140-5p 通过负调控 THY1 介导的 Notch 信号通路抑制胃癌细胞增殖、迁移,促进细胞凋亡。

MicroRNA-140-5p inhibits cell proliferation, migration and promotes cell apoptosis in gastric cancer through the negative regulation of THY1-mediated Notch signaling.

机构信息

Medical College of Nanchang University, Nanchang 330006, P.R. China.

Department of Surgery, Jiangxi Tumor Hospital, Nanchang 330029, P.R. China.

出版信息

Biosci Rep. 2019 Jul 23;39(7). doi: 10.1042/BSR20181434. Print 2019 Jul 31.

Abstract

Studies have highlighted the importance of microRNAs (miRs) in the development of various cancers, including gastric cancer (GC), a commonly occurring malignancy, accompanied by high recurrence and metastasis rate. The aim of the current study was to investigate the role of miR-140-5p in GC. Microarray expression profiles were initially employed to screen the differentially expressed gene related to GC, and the miR regulating the gene was predicted accordingly. The data obtained indicated that thymus cell antigen 1 () was differentially expressed in GC and confirmed to be a target gene of miR-140-5p. Poorly expressed miR-140-5p and highly expressed were observed in the GC tissues. SGC-7901 cells were treated with miR-140-5p mimic/inhibitor, siRNA against and siRNA against in order to determine their regulatory roles in GC cell activities. The relationship of miR-140-5p, and the Notch signaling pathway was subsequently identified. Moreover, cell proliferation, migration, invasion and apoptosis were determined using 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethonyphenol)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), wound-healing, transwell assay and flow cytometry, respectively. The overexpression of miR-140-5p and silencing of resulted in a diminished expression of the Notch signaling pathway-related proteins, as well as inhibited proliferation, migration and invasion of GC cells, enhanced expression of pro-apoptotic proteins in addition to elevated apoptosis rate. Taken together, the present study suggests that miR-140-5p directly targets and negatively regulates expression and inhibits activation of the Notch signaling pathway, whereby the up-regulation of miR-140-5p inhibits development of GC, highlighting the promise of miR-140-5p as a potential target for GC treatment.

摘要

研究强调了 microRNAs(miRs)在各种癌症发展中的重要性,包括胃癌(GC),这是一种常见的恶性肿瘤,伴有高复发和转移率。本研究旨在探讨 miR-140-5p 在 GC 中的作用。最初采用微阵列表达谱筛选与 GC 相关的差异表达基因,并相应预测调节该基因的 miR。获得的数据表明,胸腺细胞抗原 1()在 GC 中差异表达,并证实其为 miR-140-5p 的靶基因。GC 组织中观察到 miR-140-5p 表达水平低,而表达水平高。用 miR-140-5p 模拟物/抑制剂、针对的 siRNA 和针对的 siRNA 处理 SGC-7901 细胞,以确定它们在 GC 细胞活性中的调节作用。随后确定了 miR-140-5p、和 Notch 信号通路之间的关系。此外,使用 3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲基甲氧基苯基)-2-(4-磺基苯基)-2H-四唑(MTS)、划痕愈合、transwell 测定和流式细胞术分别测定细胞增殖、迁移、侵袭和凋亡。miR-140-5p 的过表达和的沉默导致 Notch 信号通路相关蛋白的表达减少,同时抑制 GC 细胞的增殖、迁移和侵袭,增加促凋亡蛋白的表达并提高凋亡率。综上所述,本研究表明 miR-140-5p 可直接靶向并负调控的表达,抑制 Notch 信号通路的激活,上调 miR-140-5p 抑制 GC 的发展,突出了 miR-140-5p 作为 GC 治疗潜在靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0bd/6646234/4c15db2a8d13/bsr-39-bsr20181434-g1.jpg

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