miR-203 suppresses pancreatic cancer cell proliferation and migration by modulating DUSP5 expression

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS
Zekiye Altan, Yunus Sahin
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引用次数: 10

Abstract

Background

Pancreatic cancer (PC) is an insidious cancer that is commonly diagnosed in advanced stages. Therefore, it is necessary to understand PC-related mechanisms in order to discover new and reliable diagnostic biomarkers. It is known that miRNAs play a crucial role in carcinogenesis by targeting mRNAs. In this study we aimed to explore interaction between downregulated miR-203 and its upregulated target DUSP5 in PC.

Methods

Using bioinformatics approaches we identified the DUSP5 as a direct target gene of miR-203 and detected potential binding sites between miR-203 and DUSP5. Additionally, we evaluated subcellular location, expression level and prognostic value of DUSP5 in PC through using various bioinformatics tools. To investigate the relationship between miR-203 and DUSP5, we increased the expression levels of miR-203 by transfecting miR-203 mimics into the pancreatic cancer cell line, PANC-1. Finally, MTT, wound healing, and colony formation assays were performed to determine effect of overexpressed miR-203 on proliferation and migration of PANC-1 cells.

Results

We found that expression level of DUSP5 in pancreas tissue was one of the lowest tissue expression among all normal human tissue types. In addition, DUSP5 expression was upregulated both PC tissues and cell line and associated with poor overall survival in PC. Overexpression of miR-203 significantly downregulated expression level of DUSP5 and remarkably suppressed proliferation, migration and colony formation ability of PANC-1 cells.

Conclusions

These findings suggest that miR-203 restrains proliferation and migration of PC cells by regulating oncogenic activity of DUSP5 in PC, thereby could be novel candidate biomarkers for PC diagnosis and treatment.

Abstract Image

miR-203通过调控DUSP5的表达抑制胰腺癌细胞的增殖和迁移
胰腺癌(PC)是一种隐匿的癌症,通常在晚期被诊断出来。因此,有必要了解pc相关机制,以发现新的可靠的诊断生物标志物。众所周知,miRNAs通过靶向mrna在癌变中起着至关重要的作用。在这项研究中,我们旨在探讨下调的miR-203与其上调的靶点DUSP5在PC中的相互作用。方法利用生物信息学方法确定DUSP5是miR-203的直接靶基因,并检测miR-203与DUSP5之间的潜在结合位点。此外,我们通过各种生物信息学工具评估了DUSP5在PC中的亚细胞定位、表达水平和预后价值。为了研究miR-203与DUSP5之间的关系,我们通过将miR-203模拟物转染到胰腺癌细胞系PANC-1中来提高miR-203的表达水平。最后,通过MTT、伤口愈合和集落形成实验来确定过表达的miR-203对PANC-1 细胞增殖和迁移的影响。结果DUSP5在胰腺组织中的表达水平是人体正常组织中表达水平最低的组织之一。此外,在PC组织和细胞系中,DUSP5的表达均上调,并与PC中较差的总生存率相关。过表达miR-203可显著下调DUSP5的表达水平,显著抑制PANC-1 细胞的增殖、迁移和集落形成能力。结论miR-203可能通过调控DUSP5在PC中的致癌活性来抑制PC细胞的增殖和迁移,可能成为诊断和治疗PC的新的候选生物标志物。
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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
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