Upregulated Solute Carrier SLC39A1 Promotes Gastric Cancer Proliferation and Indicates Unfavorable Prognosis.

IF 1.4 4区 生物学 Q4 GENETICS & HEREDITY Genetics research Pub Date : 2022-01-01 DOI:10.1155/2022/1256021
Dan Yu, Yong Chen, Ming Luo, Yanjin Peng, Shengen Yi
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引用次数: 1

Abstract

Backgrounds: Solute carrier 39A1 (SLC39A1) is an indirect zinc transporter which showed diverse tumor-related functions in different malignancies. Here, we aimed to investigate its expression and role in gastric adenocarcinoma.

Methods: A retrospective gastric adenocarcinoma cohort (n = 154) was collected from our hospital to test their tissue expression of SLC39A1 through immunohistochemical staining method. After SLC39A1 overexpression or knockdown, proliferation and invasion assays were conducted for proliferation and invasion estimation, respectively. Xenograft in nude mice was used as the in vivo strategy to validate in vitro findings.

Results: Compared with adjacent stomach tissues, gastric adenocarcinoma tissues showed significantly higher SLC39A1 on both mRNA and protein levels. Higher SLC39A1 was observed in patients with larger tumor size (P=0.003) and advanced tumor stages (P < 0.001). Univariate (P=0.001) and multivariate analyses (P=0.035) confirmed the independent prognostic significance of SLC39A1 on gastric adenocarcinoma outcomes. The median survival time was 22.0 months in patients with high-SLC39A1 expression, while up to 57.0 months in those with low-SLC39A1 (P=0.001). In vitro and in vivo assays demonstrated that overexpressing SLC39A1 could promote gastric cancer growth and invasion, while silencing SLC39A1 led to opposite effects.

Conclusions: Aberrant high-SLC39A1 expression can serve as an independent unfavorable prognostic factor for gastric adenocarcinoma. High SLC39A1 is critical for a more aggressive tumor phenotype by promoting cell proliferation and invasion. Therefore, targeting SLC39A1 may provide novel therapeutic insights.

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溶质载体SLC39A1上调促进胃癌增殖并预示不良预后。
背景:溶质载体39A1 (SLC39A1)是一种间接的锌转运蛋白,在不同的恶性肿瘤中表现出不同的肿瘤相关功能。本研究旨在探讨其在胃腺癌中的表达及其作用。方法:回顾性收集我院胃腺癌患者154例,采用免疫组化染色法检测SLC39A1的组织表达。SLC39A1过表达或敲低后,分别进行增殖和侵袭实验,估计增殖和侵袭。裸鼠的异种移植被用作体内策略来验证体外研究结果。结果:与邻近胃组织相比,胃腺癌组织中SLC39A1 mRNA和蛋白水平均显著升高。SLC39A1在肿瘤大小较大(P=0.003)和肿瘤分期较晚(P < 0.001)的患者中较高。单因素分析(P=0.001)和多因素分析(P=0.035)证实了SLC39A1对胃腺癌预后的独立预后意义。slc39a1高表达患者的中位生存时间为22.0个月,slc39a1低表达患者的中位生存时间为57.0个月(P=0.001)。体外和体内实验表明,过表达SLC39A1可以促进胃癌的生长和侵袭,而沉默SLC39A1则相反。结论:slc39a1异常高表达可作为胃腺癌的独立不良预后因素。高SLC39A1通过促进细胞增殖和侵袭,对更具侵袭性的肿瘤表型至关重要。因此,靶向SLC39A1可能提供新的治疗见解。
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来源期刊
Genetics research
Genetics research 生物-遗传学
自引率
6.70%
发文量
74
审稿时长
>12 weeks
期刊介绍: Genetics Research is a key forum for original research on all aspects of human and animal genetics, reporting key findings on genomes, genes, mutations and molecular interactions, extending out to developmental, evolutionary, and population genetics as well as ethical, legal and social aspects. Our aim is to lead to a better understanding of genetic processes in health and disease. The journal focuses on the use of new technologies, such as next generation sequencing together with bioinformatics analysis, to produce increasingly detailed views of how genes function in tissues and how these genes perform, individually or collectively, in normal development and disease aetiology. The journal publishes original work, review articles, short papers, computational studies, and novel methods and techniques in research covering humans and well-established genetic organisms. Key subject areas include medical genetics, genomics, human evolutionary and population genetics, bioinformatics, genetics of complex traits, molecular and developmental genetics, Evo-Devo, quantitative and statistical genetics, behavioural genetics and environmental genetics. The breadth and quality of research make the journal an invaluable resource for medical geneticists, molecular biologists, bioinformaticians and researchers involved in genetic basis of diseases, evolutionary and developmental studies.
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