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微小RNA-144-3p通过靶向PBX3抑制上皮-间质转化来抑制胃癌进展。

MicroRNA-144-3p suppresses gastric cancer progression by inhibiting epithelial-to-mesenchymal transition through targeting PBX3.

作者信息

Li Butian, Zhang Shengping, Shen Hao, Li Chenglong

机构信息

Department of General Surgery, Jing'an District Centre Hospital of Shanghai of Fudan University, Huashan Hospital Jing'an Branch of Fudan University, Shanghai, China.

Department of General Surgery, Jing'an District Centre Hospital of Shanghai of Fudan University, Huashan Hospital Jing'an Branch of Fudan University, Shanghai, China.

出版信息

Biochem Biophys Res Commun. 2017 Mar 4;484(2):241-247. doi: 10.1016/j.bbrc.2017.01.084. Epub 2017 Jan 19.

Abstract

MicroRNAs are aberrantly expressed in a wide variety of human cancers. The present study aims to elucidate the effects and molecular mechanisms of miR-144-3p that underlie gastric cancer (GC) development. It was observed that miR-144-3p expression was significantly decreased in GC tissues compared to that in paired non-tumor tissues; moreover, its expression was lower in tissues of advanced stage and larger tumor size, as well as in lymph node metastasis tissues compared to that in control groups. miR-144-3p expression was associated with depth of invasion (P = 0.030), tumor size (P = 0.047), lymph node metastasis (P = 0.047), and TNM stage (P = 0.048). Additionally, miR-144-3p significantly inhibited proliferation, migration, and invasion in GC cells. It also reduced F-actin expression and suppressed epithelial-to-mesenchymal transition (EMT) in GC cells. Furthermore, pre-leukemia transcription factor 3 (PBX3) was a direct target gene of miR-144-3p. PBX3 was overexpressed in GC tissues and promoted EMT in GC cells. The effects of miR-144-3p mimics or inhibitors on cell migration, invasion, and proliferation were reversed by PBX3 overexpression or downregulation respectively. These results suggest that miR-144-3p suppresses GC progression by inhibiting EMT through targeting PBX3.

摘要

微小RNA在多种人类癌症中表达异常。本研究旨在阐明miR-144-3p在胃癌(GC)发生发展中的作用及分子机制。研究发现,与配对的非肿瘤组织相比,GC组织中miR-144-3p表达显著降低;此外,与对照组相比,其在晚期、肿瘤体积较大以及淋巴结转移组织中的表达更低。miR-144-3p表达与浸润深度(P = 0.030)、肿瘤大小(P = 0.047)、淋巴结转移(P = 0.047)及TNM分期(P = 0.048)相关。此外,miR-144-3p显著抑制GC细胞的增殖、迁移和侵袭。它还降低了F-肌动蛋白的表达并抑制了GC细胞的上皮-间质转化(EMT)。此外,前白血病转录因子3(PBX3)是miR-144-3p的直接靶基因。PBX3在GC组织中过表达并促进GC细胞的EMT。miR-144-3p模拟物或抑制剂对细胞迁移、侵袭和增殖的影响分别被PBX3的过表达或下调所逆转。这些结果表明,miR-144-3p通过靶向PBX3抑制EMT来抑制GC进展。

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