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miR-206高表达预示不良预后:食管癌的潜在治疗靶点

High Expression of miR-206 Predicts Adverse Outcomes: A Potential Therapeutic Target for Esophageal Cancer.

作者信息

Du Guobo, Zhou Jing, Cheng Long, Ma Xiaojie, Gui Yan, Tan Bangxian

机构信息

Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan 637000, China.

Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan 637000, China.

出版信息

Comb Chem High Throughput Screen. 2019;22(9):599-611. doi: 10.2174/1386207322666191018145825.

Abstract

BACKGROUND

MicroRNA-206 (miR-206) inhibits cell proliferation, invasion and migration in a variety of tumors, but the prognostic value of its Esophageal Cancer (EC) remains unclear.

OBJECTIVE

To study the role of miR-206 in EC.

METHODS

The datasets of RNA-Seq, miRNA-Seq, methylation, copy number variation (CNV), and clinical follow-up information were download from The Cancer Genome Atlas (TCGA). After integration and standardization, the prognostic value and potential function of miR-206 were analyzed. The important roles of miR-206 expression in EC genetic and epigenetic mechanisms were analyzed by RNA-Seq, miRNA-Seq, and methylation data. The potential mechanism of CNV in different miR-206 expression groups was analyzed using GISTIC.

RESULTS

High expression of miR-206 was associated with poor outcome of EC (OS: p=0.005, AUC=0.69, N=178). Transforming growth factor β (TGF-β) signaling pathway, Wnt signaling pathway, mitogen-activated protein kinases (MAPK) signaling pathway, mammalian target of rapamycin (mTOR) signaling pathway were inhibited in high expression group. the aberrant methylation sites in the high and low expression groups were mainly distributed in the promoter region containing CpG islands, and there were different copy number patterns in the H and L samples, and the genes in the differential copy number were mainly enriched in cancer-related pathways, such as thyroid cancer, central carbon metabolism.

CONCLUSION

This study explored the unique genomic and epigenetic landscape associated with the expression of miR-206, provided evidence of mir-206 as a prognostic biomarker or a potential therapeutic target for EC patients.

摘要

背景

微小RNA-206(miR-206)在多种肿瘤中抑制细胞增殖、侵袭和迁移,但其在食管癌(EC)中的预后价值仍不清楚。

目的

研究miR-206在EC中的作用。

方法

从癌症基因组图谱(TCGA)下载RNA测序、miRNA测序、甲基化、拷贝数变异(CNV)和临床随访信息数据集。经过整合和标准化后,分析miR-206的预后价值和潜在功能。通过RNA测序、miRNA测序和甲基化数据,分析miR-206表达在EC遗传和表观遗传机制中的重要作用。使用GISTIC分析不同miR-206表达组中CNV的潜在机制。

结果

miR-206高表达与EC预后不良相关(总生存期:p=0.005,AUC=0.69,N=178)。高表达组中转化生长因子β(TGF-β)信号通路、Wnt信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、雷帕霉素靶蛋白(mTOR)信号通路受到抑制。高表达组和低表达组的异常甲基化位点主要分布在含有CpG岛的启动子区域,H和L样本存在不同的拷贝数模式,差异拷贝数中的基因主要富集在癌症相关通路,如甲状腺癌、中心碳代谢。

结论

本研究探索了与miR-206表达相关的独特基因组和表观遗传景观,为miR-206作为EC患者的预后生物标志物或潜在治疗靶点提供了证据。

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