Department of General Surgery, The Fifth Central Hospital of Tianjin, Tianjin, China.
Department of Radiology, The Fifth Central Hospital of Tianjin, Tianjin, China.
J Clin Lab Anal. 2020 Dec;34(12):e23511. doi: 10.1002/jcla.23511. Epub 2020 Aug 29.
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.
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.
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.
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.
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。
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。
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。
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。