Integrative analysis of negatively regulated miRNA-mRNA axes for esophageal squamous cell carcinoma

Abstract

BACKGROUND: MicroRNAs regulating mRNA expression by targeting at mRNAs is known constructive in tumor occurrence, immune escape, and metastasis. OBJECTIVE: This research aims at finding negatively regulatory miRNA-mRNA pairs in esophageal squamous cell carcinoma (ESCC). METHODS: GENE expression data of The Cancer Genome Atlas (TCGA) and GEO database were employed in differently expressed RNA and miRNA (DE-miRNAs/DE-mRNAs) screening. Function analysis was conducted with DAVID-mirPath. MiRNA-mRNA axes were identified by MiRTarBase and TarBase and verified in esophageal specimen by real-time reverse transcription polymerase chain reaction (RT-qPCR). Receiver operation characteristic (ROC) curve and Decision Curve Analysis (DCA) were applied in miRNA-mRNA pairs predictive value estimation. Interactions between miRNA-mRNA regulatory pairs and immune features were analyzed using CIBERSORT. RESULTS: Combining TCGA database, 4 miRNA and 10 mRNA GEO datasets, totally 26 DE-miRNAs (13 up and 13 down) and 114 DE-mRNAs (64 up and 50 down) were considered significant. MiRTarBase and TarBase identified 37 reverse regulation miRNA-mRNA pairs, 14 of which had been observed in esophageal tissue or cell line. Through analysis of RT-qPCR outcome, miR-106b-5p/KIAA0232 signature was chosen as characteristic pair of ESCC. ROC and DCA verified the predictive value of model containing miRNA-mRNA axis in ESCC. Via affecting mast cells, miR-106b-5p/KIAA0232 may contribute to tumor microenvironment. CONCLUSIONS: The diagnostic model of miRNA-mRNA pair in ESCC was established. Their complex role in ESCC pathogenesis especially tumor immunity was partly disclosed.