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微小RNA-454-3p通过靶向胰岛素样生长因子2信使核糖核酸结合蛋白1抑制食管癌细胞的增殖和侵袭。

MicroRNA-454-3p inhibits cell proliferation and invasion in esophageal cancer by targeting insulin-like growth factor 2 mRNA-binding protein 1.

作者信息

Yan Aiting, Wang Cuizhu, Zheng Liangfeng, Zhou Jiebo, Zhang Yan

机构信息

Department of Oncology, Affiliated Haian Hospital of Nantong University, Nantong, Jiangsu 226600, P.R. China.

Central Laboratory, Affiliated Haian Hospital of Nantong University, Nantong, Jiangsu 226600, P.R. China.

出版信息

Oncol Lett. 2020 Dec;20(6):359. doi: 10.3892/ol.2020.12223. Epub 2020 Oct 14.

Abstract

Esophageal cancer (ESCA) is the eighth most common cause of cancer-associated mortality in humans. An increasing number of studies have demonstrated that microRNAs (miRs) serve important roles in mediating tumor initiation and progression. miR-454-3p has been found to be involved in the development of various human malignancies; however, little is known about the role of miR-454-3p in esophageal cancer. In the present study, the protein and gene expression levels of miR-454-3p in ESCA tissues and cells were downregulated compared with adjacent normal tissues and normal human esophageal epithelial cells. Additionally, miR-454-3p downregulation resulted in improved survival rates in patients with ESCA, and miR-454-3p overexpression significantly suppressed cell proliferation, migration and invasion and promoted apoptosis in four ESCA cell lines (EC9706, ECA109, TE-1 and TE-8). It was found that miR-454-3p overexpression inhibited the expression of insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) at the protein and mRNA expression levels. Furthermore, it was demonstrated that miR-454-3p inhibited ESCA cell proliferation, migration and apoptosis by targeting IGF2BP1 via the ERK and AKT signaling pathways in a subcutaneous xenograft tumor mouse model. These results showed that miR-454-3p functioned as an important tumor suppressor in ESCA by targeting IGFBP1. Therefore, miR-454-3p may be a novel prognostic biomarker and therapeutic target for patients with ESCA.

摘要

食管癌(ESCA)是人类癌症相关死亡的第八大常见原因。越来越多的研究表明,微小RNA(miRs)在介导肿瘤发生和发展中起重要作用。已发现miR-454-3p参与多种人类恶性肿瘤的发展;然而,关于miR-454-3p在食管癌中的作用知之甚少。在本研究中,与相邻正常组织和正常人食管上皮细胞相比,ESCA组织和细胞中miR-454-3p的蛋白质和基因表达水平下调。此外,miR-454-3p下调导致ESCA患者生存率提高,miR-454-3p过表达显著抑制四种ESCA细胞系(EC9706、ECA109、TE-1和TE-8)的细胞增殖、迁移和侵袭,并促进细胞凋亡。研究发现,miR-454-3p过表达在蛋白质和mRNA表达水平上抑制胰岛素样生长因子2 mRNA结合蛋白1(IGF2BP1)的表达。此外,在皮下异种移植肿瘤小鼠模型中证明,miR-454-3p通过ERK和AKT信号通路靶向IGF2BP1抑制ESCA细胞增殖、迁移和凋亡。这些结果表明,miR-454-3p通过靶向IGFBP1在ESCA中发挥重要的肿瘤抑制作用。因此,miR-454-3p可能是ESCA患者的一种新型预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb07/7590437/185e1688e4e5/ol-20-06-12223-g00.jpg

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