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miR-212 作为一种潜在的生物标志物,通过靶向 SOX4 抑制胃癌的增殖。

miR-212 as potential biomarker suppresses the proliferation of gastric cancer via targeting SOX4.

机构信息

Department of General Surgery, The Fifth Central Hospital of Tianjin, Tianjin, China.

Department of Radiology, The Fifth Central Hospital of Tianjin, Tianjin, China.

出版信息

J Clin Lab Anal. 2020 Dec;34(12):e23511. doi: 10.1002/jcla.23511. Epub 2020 Aug 29.

Abstract

BACKGROUND

Circulating microRNAs that post-transcriptionally regulate gene expressions have been reported as promising biomarkers in cancer monitoring. This study was to identify the potential role of circulating miR-212 in gastric cancer and whether it could serve as a novel biomarker for gastric cancer.

METHODS

We detected the serum levels of miR-212 in 100 health people and 110 gastric cancer patients and analyzed the relationships of the serum level of miR-212 with gastric cancer. We detected the expression of miR-212 in human gastric mucosal epithelial cell line (GES-1) and human gastric cancer cell lines (NCI-N87 and SNU-16) using qRT-PCR. Then, we detected the role of 5-aza-deoxycytidine on the epigenetic regulation of miR-212 in human gastric cancer cell lines. Furthermore, luciferase reporter assay was used to detect binding activity of miR-212 on SOX4 mRNA, and their functions on the cell proliferation and apoptosis.

RESULTS

The expression of miR-212 was higher in health people than that in gastric cancer patients, higher in gastric mucosal epithelial cell line than that in gastric cancer cells. miR-212 can be a circulating biomarker and an independent prognostic factor of gastric cancer. Moreover, miR-212 can directly regulate the 3'UTR of SOX4 mRNA to suppress p53 and Bax, resulting gastric cancer cells proliferation inhibition and apoptosis induction.

CONCLUSION

Our study demonstrated that miR-212 was epigenetically downregulated in gastric cancer, and resulting low level of miR-212 can be a potential circulating biomarker and poor prognosis predicator of gastric cancer.

摘要

背景

已报道循环 microRNAs 通过转录后调控基因表达,作为癌症监测的有前途的生物标志物。本研究旨在鉴定循环 miR-212 在胃癌中的潜在作用,以及其是否可作为胃癌的新型生物标志物。

方法

我们检测了 100 名健康人和 110 名胃癌患者的血清 miR-212 水平,并分析了血清 miR-212 水平与胃癌的关系。我们使用 qRT-PCR 检测了人胃黏膜上皮细胞系(GES-1)和人胃癌细胞系(NCI-N87 和 SNU-16)中 miR-212 的表达。然后,我们检测了 5-氮杂-2'-脱氧胞苷对人胃癌细胞系中 miR-212 的表观遗传调控作用。此外,还使用荧光素酶报告基因检测法检测了 miR-212 对 SOX4 mRNA 的结合活性及其对细胞增殖和凋亡的功能。

结果

miR-212 在健康人群中的表达高于胃癌患者,在胃黏膜上皮细胞系中的表达高于胃癌细胞。miR-212 可以作为循环生物标志物和胃癌的独立预后因素。此外,miR-212 可以直接调节 SOX4 mRNA 的 3'UTR,抑制 p53 和 Bax,从而抑制胃癌细胞的增殖并诱导其凋亡。

结论

本研究表明,miR-212 在胃癌中呈表观遗传下调,其低水平可能是胃癌的潜在循环生物标志物和不良预后预测因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3880/7755761/5f3656e41930/JCLA-34-e23511-g001.jpg

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