Abstract
We analyzed data from two non-coding RNA profiling arrays made available by the Gene Expression Omnibus (GEO) and found 17 miRNAs with remarkable differential expression between malignant and normal esophageal tissue. Correlation analysis between expression of these 17 miRNAs and patients’ clinicopathological characteristics showed that miR-203 was down-regulated in esophageal carcinoma (EC) tissues and was significantly associated with lymph node metastasis and poor overall survival. Overexpression of miR-203 significantly attenuated cellular proliferation, migration and invasion by EC cells in culture. Additionally, gene expression profiles and bioinformatics analysis revealed KIF5C to be a direct target of miR-203, and KIF5C overexpression partially counteracted the tumor inhibitory effects of miR-203 on EC cells. We also observed that miR-203, reduced KIFC5 protein levels, promoted cytoplasmic accumulation of Axin2, and reversed the invasive phenotype of EC cells. Taken together, these data demonstrate that miR-203 is a tumor suppressor in EC cells and its expression level could potentially be used as a prognostic indicator for EC patient outcomes.
Highlights
esophageal carcinoma (EC) is one of the most common cancers worldwide [1, 2]; due to a high incidence of recurrence, its prognosis is poor [3]. miRNAs play a critical role in regulating tumorigenesis and metastasis of EC [4, 5], and some miRNAs have been identified as prognostic markers or potential therapeutic targets [6, 7]. miRNAs can act as either oncogenes or tumor suppressors to modulate growth, angiogenesis, drug or chemoresistance, invasion, and metastasis of malignant cells [8, 9]
We first analyzed data from two non-coding RNA profiling arrays released by Gene Expression Omnibus (GEO) to reveal 17 miRNAs with significant differential expression between malignant and normal esophageal tissue, including miR-98, miR133, and miR-30a-3
Bioinformatics, and correlation analysis, we demonstrated that KIF5C may be the direct target of miR-203 in EC cells
Summary
EC is one of the most common cancers worldwide [1, 2]; due to a high incidence of recurrence, its prognosis is poor [3]. miRNAs play a critical role in regulating tumorigenesis and metastasis of EC [4, 5], and some miRNAs have been identified as prognostic markers or potential therapeutic targets [6, 7]. miRNAs can act as either oncogenes or tumor suppressors to modulate growth, angiogenesis, drug or chemoresistance, invasion, and metastasis of malignant cells [8, 9]. MiRNAs play a critical role in regulating tumorigenesis and metastasis of EC [4, 5], and some miRNAs have been identified as prognostic markers or potential therapeutic targets [6, 7]. A systematic non-coding RNA profiling array and miRNA-seq evaluation in EC development may implicate certain miRNAs as prognostic markers and reveal potential therapeutic targets. We used non-coding RNA profiling array data released by GEO [13] to identify miRNAs differentially expressed between malignant and normal esophageal tissue. We performed correlation analysis with clinicopathological and miRNA-sequencing data of tumor tissues released by the Cancer Genome Atlas (TCGA) [14] to find miRNAs with significantly altered expression in esophageal carcinoma tissues and evaluated correlations to patient outcomes in order to find predictors for EC prognostic evaluation
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