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

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.

Keywords: Bioinformatics; CNV; esophageal cancer; miR-206; multi-omics analysis; the cancer genome atlas..