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微小RNA-493通过靶向RhoC抑制胃癌细胞的增殖和侵袭。

MiR-493 suppresses the proliferation and invasion of gastric cancer cells by targeting RhoC.

作者信息

Zhou Wenhua, Zhang Chi, Jiang Hao, Zhang Zhiwei, Xie Liming, He Xiusheng

机构信息

Cancer Research Institute, University of South China, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Hengyang, People's Republic of China.

Function Laboratory Center, Medical School, University of South China, Hengyang, Hunan, People's Republic of China.

出版信息

Iran J Basic Med Sci. 2015 Oct;18(10):1027-33.

Abstract

OBJECTIVES

MiRNAs have been proposed to be key regulators of tumorigenesis, progression and metastasis. However, their effect and prognostic value in gastric cancer is still poorly known.

MATERIALS AND METHODS

Gastric cancer cell lines were cultured. Tissue samples obtained from 36 gastric cancer patients were used for quantitative real-time PCR (qRT-PCR) analysis. The tissue microarrays (TMAs) consisted of 126 cases of gastric carcinoma that were used for In situ hybridisation (ISH). Lentivirus plasmids were co-transfected into 293FT cells. Cell migration was examined using wound-healing assays. Statistical analyses were performed using SPSS16.0 software.

RESULTS

In this study, we found that the expression levels of miR-493 were strongly down-regulated in gastric cancer and were associated with clinical stage and the presence of lymph node metastases. Moreover, miR-493 might independently predict OS and RFS in gastric cancer. We further found that up-regulation of miR-493 inhibited the proliferation and metastasis of gastric cancer cells, in vitro and in vivo. In addition, miR-493 directly targeted RhoC, which resulted in a marked reduction of the expression of mRNA and protein. This effect, in turn, led to a decreased ability of growth, invasion and metastasis in gastric cancer cells.

CONCLUSION

Taken together, our findings demonstrate that miR-493 is important for gastric cancer initiation and progression and holds promise as a prognostic biomarker to predict survival and relapse in gastric cancer. It is also a potential therapeutic tool to improve clinical outcomes in this disease.

摘要

目的

微小RNA(miRNAs)被认为是肿瘤发生、进展和转移的关键调节因子。然而,它们在胃癌中的作用和预后价值仍知之甚少。

材料与方法

培养胃癌细胞系。从36例胃癌患者获取的组织样本用于定量实时聚合酶链反应(qRT-PCR)分析。组织芯片(TMAs)由126例胃癌病例组成,用于原位杂交(ISH)。慢病毒质粒共转染至293FT细胞。采用伤口愈合试验检测细胞迁移。使用SPSS16.0软件进行统计分析。

结果

在本研究中,我们发现miR-493的表达水平在胃癌中显著下调,且与临床分期和淋巴结转移的存在相关。此外,miR-493可能独立预测胃癌的总生存期(OS)和无复发生存期(RFS)。我们进一步发现,上调miR-493在体外和体内均抑制胃癌细胞的增殖和转移。此外,miR-493直接靶向RhoC,导致mRNA和蛋白表达明显降低。这种效应进而导致胃癌细胞生长、侵袭和转移能力下降。

结论

综上所述,我们的研究结果表明,miR-493对胃癌的发生和进展至关重要,有望作为预测胃癌生存和复发的预后生物标志物。它也是改善该疾病临床结局的潜在治疗工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/466e/4686574/c631192b9892/IJBMS-18-1027-g001.jpg

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