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Menin通过与IQGAP1相互作用来抑制胃癌细胞的增殖。

Menin represses the proliferation of gastric cancer cells by interacting with IQGAP1.

作者信息

Ren Feng, Guo Qin, Zhou Huan

机构信息

Department of Clinical Laboratory, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.

Department of Blood Transfusion, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.

出版信息

Biomed Rep. 2023 Feb 17;18(4):27. doi: 10.3892/br.2023.1609. eCollection 2023 Apr.

Abstract

The multiple endocrine neoplasia type 1 gene coding the protein menin was originally identified in patients with multiple endocrine tumors, and is mainly expressed in the cell nucleus. Multiple lines of evidence have indicated that menin acts as a tumor suppressor protein interacting with other various proteins. The mechanism of menin inhibiting tumorigenesis remains unclear. The present study analyzed the expression of menin and IQ motif-containing GTPase-activating protein 1 (IQGAP1) proteins in gastric cancer tissues and cell lines, and investigated the association between these two molecules. Western blotting was used to determine the quantity of target proteins. Cell proliferation was measured using MTT assay. It was found that the protein expression of menin was lower in gastric cancer tissues and AGS cells, while the protein expression of IQGAP1 was higher, compared with the levels observed in normal tissues and GES-1 cells. Ectopic expression of IQGAP1 stimulated the proliferation of gastric cancer cells, but did not affect the expression of menin. However, overexpression of menin inhibited the proliferation of gastric cancer cells. The inhibition was partly achieved through inhibiting the expression of IQGAP1, which was accompanied by inhibition of PI3K and NF-κB expression. Taken together, the present results suggest a novel function for menin and IQGAP1 contributing to suppress the proliferation of gastric cancer cells.

摘要

编码蛋白menin的多发性内分泌肿瘤1型基因最初是在患有多发性内分泌肿瘤的患者中发现的,且主要在细胞核中表达。多项证据表明,menin作为一种肿瘤抑制蛋白,可与其他多种蛋白质相互作用。menin抑制肿瘤发生的机制尚不清楚。本研究分析了menin和含IQ模体的GTP酶激活蛋白1(IQGAP1)在胃癌组织和细胞系中的表达,并研究了这两种分子之间的关联。采用蛋白质印迹法测定靶蛋白的量。使用MTT法测量细胞增殖。结果发现,与正常组织和GES-1细胞中的水平相比,menin的蛋白表达在胃癌组织和AGS细胞中较低,而IQGAP1的蛋白表达较高。IQGAP1的异位表达刺激了胃癌细胞的增殖,但不影响menin的表达。然而,menin的过表达抑制了胃癌细胞的增殖。这种抑制部分是通过抑制IQGAP1的表达实现的,同时伴随着PI3K和NF-κB表达的抑制。综上所述,目前的结果表明menin和IQGAP1具有抑制胃癌细胞增殖的新功能。

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