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TCF12激活MAGT1表达以调节胰腺癌细胞的恶性进展。

TCF12 activates MAGT1 expression to regulate the malignant progression of pancreatic carcinoma cells.

作者信息

Wang Ling, Tang Yanjiao, Wu Hongyi, Shan Guiqiu

机构信息

Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250014, P.R. China.

Medical Laboratory, Shenzhen Sami Medical Center, Shenzhen, Guangdong 518038, P.R. China.

出版信息

Oncol Lett. 2022 Feb;23(2):62. doi: 10.3892/ol.2021.13180. Epub 2021 Dec 27.

Abstract

As a highly malignant gastrointestinal tumor, pancreatic carcinoma (PC) has poor prognosis due to its low early diagnosis rate, advanced tumor resection and chemotherapy resistance. Magnesium transporter 1 (MAGT1) is a magnesium ion transporter located on the cell membrane, which shows promotive effects on biological behaviors of multiple tumor cells. The aim of the present study was to investigate the role of MAGT1 in the progression of PC and its potential molecular mechanism. Based on the Gene Expression Profiling Interactive Analysis website, MAGT1 was highly expressed in tissues from patients with PC and was associated with poor prognosis. In functional experiments, MAGT1 was highly expressed in PC cell lines. The Cell Counting Kit-8, gap closure and Transwell assays, and western blot analysis, were used to investigate the effects of MAGT1 overexpression or knockdown on the biological behaviors of PC cells. It was found that MAGT1 promoted the proliferation, migration and invasion of PC cells . According to the Encyclopedia of RNA Interactomes website, transcription factor 12 (TCF12) mRNA expression level was positively correlated with MAGT1 expression level in the tissues from patients with PC. Positive targeting regulation of MAGT1 by TCF12 was also confirmed using a dual-luciferase gene reporter assay and chromatin immunoprecipitation. In addition, knockdown of TCF12 expression inhibited the proliferation and migration of PC cells, but overexpression of MAGT1 expression partly reversed this. These results suggested that TCF12 could promote the proliferation, migration and invasion of PC cells by activating MAGT1 expression, which was associated with poor prognosis. These findings suggest that MAGT1 could be a promising biomarker for the occurrence, progression and prognosis of PC.

摘要

作为一种高度恶性的胃肠道肿瘤,胰腺癌(PC)由于早期诊断率低、肿瘤切除进展以及化疗耐药性,预后较差。镁转运蛋白1(MAGT1)是一种位于细胞膜上的镁离子转运蛋白,对多种肿瘤细胞的生物学行为具有促进作用。本研究的目的是探讨MAGT1在PC进展中的作用及其潜在的分子机制。基于基因表达谱交互式分析网站,MAGT1在PC患者的组织中高表达,且与预后不良相关。在功能实验中,MAGT1在PC细胞系中高表达。采用细胞计数试剂盒-8、划痕愈合和Transwell实验以及蛋白质免疫印迹分析,研究MAGT1过表达或敲低对PC细胞生物学行为的影响。发现MAGT1促进了PC细胞的增殖、迁移和侵袭。根据RNA相互作用组百科全书网站,在PC患者的组织中,转录因子12(TCF12)mRNA表达水平与MAGT1表达水平呈正相关。使用双荧光素酶基因报告实验和染色质免疫沉淀也证实了TCF12对MAGT1的正向靶向调控。此外,敲低TCF12表达抑制了PC细胞的增殖和迁移,但MAGT1表达的过表达部分逆转了这一现象。这些结果表明,TCF12可通过激活MAGT1表达促进PC细胞的增殖、迁移和侵袭,这与预后不良相关。这些发现提示,MAGT1可能是PC发生、进展和预后的一个有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68e1/8756560/07a15281c26e/ol-23-02-13180-g00.jpg

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