High expression of TMEM40 contributes to progressive features of tongue squamous cell carcinoma.

High expression of TMEM40 contributes to progressive features of tongue squamous cell carcinoma.
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TMEM40的高表达有助于舌鳞状细胞癌的进展特征

DOI:
10.3892/or.2018.6788
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发表时间:
2019-01
期刊:
影响因子:
4.2
通讯作者:
Shi R
Shi R
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Q;Huang D;Zhang Z;Feng Y;Fu M;Wei M;Zhou J;Huang Y;Liu S;Shi R

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跨膜蛋白 40 (TMEM40) 是一种 23 kDa 的蛋白,其与舌鳞状细胞癌 (TSCC) 的关系仍不清楚。本研究旨在探讨TMEM40在TSCC中的表达、临床意义及其在TSCC细胞中的作用。采用免疫组化方法检测60份舌组织样本中TMEM40的表达水平。此外,通过分别转染 pEZ-M98-TMEM40 质粒或 TMEM40 小干扰 RNA,TMEM40 在两种 TSCC 细胞系中过表达并受到抑制。使用细胞计数试剂盒-8和集落形成实验分别研究TMEM40对细胞增殖和集落形成能力的影响。进行流式细胞术以确定转染细胞的细胞凋亡和周期状况。通过伤口愈合和 Transwell 实验分别探讨 TMEM40 对细胞迁移和侵袭的影响。结果表明,与癌旁正常舌组织相比,TSCC组织中TMEM40的表达量显着升高(P<0.01)。临床病理分析显示,TMEM40表达与病理TNM(pTNM)状态(P<0.05)、组织学分级(P<0.001)和临床分期(P<0.01)呈正相关,但与性别、年龄无关。细胞增殖、凋亡、迁移和侵袭测定的结果表明,当TMEM40在CAL27和SCC9 TSCC细胞系中成功过表达或敲低时,TMEM40过表达细胞中的细胞生长和侵袭增加,而TMEM40敲低细胞中的细胞生长和侵袭减少。此外,实验表明TMEM40敲低导致p53和Bax水平升高,MMP-9水平降低,这表明TMEM40通过参与p53、Bax和MMP-9来调节TSCC细胞的细胞凋亡和迁移。我们的研究结果表明,TMEM40 表达的增加通过调节 p53、Bax 和 MMP-9 促进 TSCC 的进展特征。
Transmembrane protein 40 (TMEM40) is a 23-kDa protein and its association with tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the expression and clinical significance of TMEM40 in TSCC and its roles in TSCC cells. Immunohistochemical analysis was performed to detect the expression levels of TMEM40 in 60 tongue tissue samples. Furthermore, TMEM40 was overexpressed and inhibited in two TSCC cell lines by transfection with pEZ-M98-TMEM40 plasmid or TMEM40 small interfering RNA, respectively. Cell Counting Kit-8 and colony formation assays were used to investigate the effects of TMEM40 on cell proliferation and colony formation ability, respectively. Flow cytometry was performed to determine cell apoptosis and cycle conditions of transfected cells. Wound-healing and Transwell assays were processed to explore the effects of TMEM40 on cell migration and invasion, respectively. The results indicated that TMEM40 expression levels were significantly increased in TSCC tissues compared with adjacent normal tongue tissues (P<0.01). Clinicopathological analysis revealed that TMEM40 expression was positively correlated with pathological TNM (pTNM) status (P<0.05), histological grade (P<0.001) and clinical stage (P<0.01), but not with sex or age. Results of cell proliferation, apoptosis, migration and invasion assays indicated that when TMEM40 had been successfully overexpressed or knocked down in CAL27 and SCC9 TSCC cell lines, cell growth and invasion increased in the TMEM40 overexpressing cells, while they decreased in TMEM40-knockdown cells. Furthermore, experiments revealed that TMEM40 knockdown resulted in increased levels of p53 and Bax, and decreased levels of MMP-9, which indicated that TMEM40 regulated cell apoptosis and migration via involvement of p53, Bax and MMP-9 in TSCC cells. Our findings indicated that increased expression of TMEM40 contributed to progressive features of TSCC via regulation of p53, Bax and MMP-9.
DOI: 10.1016/j.molcel.2015.06.029
发表时间: 2015-08-20
期刊: Molecular cell
影响因子: 16
作者:
Follis AV;Llambi F;Merritt P;Chipuk JE;Green DR;Kriwacki RW
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