Expression and Regulatory Network Analysis of MiR-139-3p, a New Potential Serum Biomarker for Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis

Abstract

Background: In recent studies, microRNAs have been demonstrated as stable detectable biomarkers in blood for cancer. In addition, computer-aided biomarker discovery has now become an attractive paradigm for precision diagnosis. Methods: In this study, we identified and evaluated miR-139-3p as a biomarker for screening of esophageal squamous cell carcinoma using the Cancer Genome Atlas and Gene Expression Omnibus database analyses. We identified possible miR-139-3p target genes through the predicted database and esophageal squamous cell carcinoma upregulated genes from the Cancer Genome Atlas and Gene. Bioinformatics analysis was performed to determine key miR-139-3p targets and pathways associated with esophageal carcinoma. Finally, the expression and expected significance of hub genes were evaluated via the Genotype-Tissue Expression project. Results: MiR-139-3p was significantly downregulated in patients with esophageal squamous cell carcinoma/esophageal carcinoma. In GSE 122497, the area under the curve-receiver operating characteristic value, sensitivity, and specificity for serum miR-139-3p were 0.754, 67.49%, and 80.00%, respectively. The pattern specification process, skeletal system development, and regionalization process were the most enriched interactions in esophageal carcinoma. In addition, Epstein-Barr virus infection, human T-cell leukemia virus 1 infection, and human cytomegalovirus infection were identified as crucial pathways. Six hub genes (CD1A, FCGR2A, ANPEP, CD1B, membrane metalloendopeptidase, and TWIST1) were found, and FCGR2A and membrane metalloendopeptidase were further confirmed by genotype-tissue expression. High expression of membrane metalloendopeptidase correlated with a better overall survival but not with disease-free survival of patients with esophageal carcinoma. Conclusions: MiR-139-3p was identified as a candidate biomarker for predicting esophageal squamous cell carcinoma based on network analysis. MiR-139-3p acted as a tumor suppressor by targeting membrane metalloendopeptidase in esophageal carcinoma, and low expression of membrane metalloendopeptidase may indicate a better prognosis of patients with esophageal carcinoma.

Development of a prognostic nomogram based on an eight-gene signature for esophageal squamous cell carcinoma by weighted gene co-expression network analysis (WGCNA)

“…MiR-139-3p is a candidate serum biomarker for predicting the prognosis of ESCC. Previous study showed that FCGR2A could be mediated by miR-139-3p at the posttranscriptional level (25). GNGT1 can predict the response to platinum-based chemotherapy drugs (26).…”

MicroRNAs Possibly Involved in the Development of Bone Metastasis in Clear-Cell Renal Cell Carcinoma

“…A tumor suppressor role has also been described in bladder cancer [ 109 ], CRC [ 110 ], glioblastoma multiforme [ 111 ], BC [ 45 ], and HCC [ 112 ]. Additionally, miR-139-3p is downregulated in serum in patients with esophagal squamous cell cancer (SCC), highlighting its potential as a serum biomarker [ 113 ]. miR-139-5p is a regulator of osteoblast differentiation and apoptosis by targeting ELK1 and ODSM [ 44 ].…”

Long non-coding RNA BCAR4 aggravated proliferation and migration in esophageal squamous cell carcinoma by negatively regulating p53/p21 signaling pathway

“…Xia et al has been demonstrated that lncRNA TP73-AS1 reducedmiR-139-3p to promote retinoblastoma cell proliferation [ 24 ]. In addition, miR-139-3p was predicted to be acted as a tumor suppressor in ESCC [ 25 ]. Interestingly, miR-139-3p was the target of BCAR4 in our study through online bio-prediction site.…”