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microRNA‐messenger RNA regulatory network of esophageal squamous cell carcinoma and the identification of miR‐1 as a biomarker of patient survival
Author(s) -
Wei Qiao,
Li Xiyi,
Yu Weiwei,
Zhao Kuaile,
Qin Guangqi,
Chen Huan,
Gu Yanzi,
Ding Fei,
Zhu Zhengfei,
Fu Xiaolong,
Sun Menghong
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28166
Subject(s) - microrna , biology , carcinogenesis , cancer research , gene expression , regulation of gene expression , messenger rna , competing endogenous rna , gene , microarray analysis techniques , rna , long non coding rna , genetics
Emerging evidence indicates that microRNAs (miRNAs) play an important role in tumor carcinogenesis and progression by targeting gene expression. The goal of this study was to comprehensively analyze the vital functional miRNAs and their target genes in esophageal squamous cell carcinoma (ESCC) and to explore the clinical significance and mechanisms of miR‐1 in ESCC. First, the miRNA and messenger RNA (mRNA) expression profiles of ESCC were determined with microarray technology. Using an integrated analysis of miRNAs and their target genes with multistep bioinformatics methods, the miRNA‐mRNA regulatory network in ESCC was constructed. Next, miR‐1 expression in 292 ESCC patients and its relationship with clinicopathological features and prognosis were detected by in situ hybridization. Furthermore, the biological functions of miR‐1 were determined with in vitro and in vivo functional experiments. Finally, real‐time quantitative reverse transcription polymerase chain reaction, Western blot analysis, and luciferase reporter assays were performed to verify the target genes of miR‐1 . In this study, 67 miRNAs and 2992 genes were significantly differentially expressed in ESCC tissues compared with their expression in adjacent normal tissues, and an miRNA‐mRNA regulatory network comprising 59 miRNAs and 162 target mRNAs was identified. Low miR‐1 expression was correlated with pathological T stage, lymph node metastasis, vessel invasion, and poor clinical outcome. miR‐1 suppressed ESCC cell proliferation and invasion and promoted ESCC cell apoptosis. Fibronectin 1 ( FN1 ) was verified as a direct target of miR‐1 . Taken together, the present results suggest that miR‐1 may be a valuable prognostic predictor for ESCC, and the miR‐1 / FN1 axis may be a therapeutic target.