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Abstract
Purpose Accumulating evidence indicates that miRNAs (miRs) play crucial roles in the modulation of tumors development. However, the accurately mechanisms have not been entirely clarified. In this study, we aimed to explore the role of miR-200b in the development of gastric cancer (GC). Methods Western blot and RT-PCR were applied to detect epithelial-mesenchymal transition (EMT) marker expression and mRNA expression. Transwell assay was used for measuring the metastasis and invasiveness of GC cells. TargetScan system, luciferase reporter assay, and rescue experiments were applied for validating the direct target of miR-200b. Results MiR-200b was prominently decreased in GC tissues and cells, and its downregulation was an indicator of poor prognosis of GC patients. Reexpression of miR-200b suppressed EMT along with GC cell migration and invasion. Neuregulin 1 (NRG1) was validated as the target of miR-200b, and it rescued miR-200b inhibitory effect on GC progression. In GC tissues, the correlation of miR-200b with NRG1 was inverse. Conclusion MiR-200b suppressed EMT-related migration and invasion of GC through the ERBB2/ERBB3 signaling pathway via targeting NRG1.
Highlights
As a malignant tumor originating from the gastric mucosa epithelium, gastric cancer (GC) occupies the first place among various malignant tumors in China [1, 2]. e vast majority of GC belongs to adenocarcinoma, and there are no obvious symptoms at the early stage
To investigate whether miR-200b was abnormally expressed during GC metastasis, we first detected miR-200b expression in GC tissue specimens
We revealed that high expression of miR-200b predicted high overall survival time, while low expression of miR-200b served as an indicator of poor prognosis of GC patients (Figure 1(b))
Summary
As a malignant tumor originating from the gastric mucosa epithelium, gastric cancer (GC) occupies the first place among various malignant tumors in China [1, 2]. e vast majority of GC belongs to adenocarcinoma, and there are no obvious symptoms at the early stage. Accumulating evidence has shown that miRs take part in many tumors development, including migration and invasion. MiR-214 was decreased in GC, and its downregulation contributed to GC cell migration and invasion via inducing EMT [9]. MiR-1292 suppressed GC cell invasion and migration via DEK [10]. The molecular mechanism of miR-200b in the modulation of GC invasion and migration has not been fully clarified. Epithelial-mesenchymal transition (EMT) plays important roles in the metastasis of various cancers, and it is an important biological process in which epidermal malignant cells acquire the ability to migrate and invade [12,13,14]. Us, understanding the mechanism of miR-200b in regulating EMT is very important Epithelial-mesenchymal transition (EMT) plays important roles in the metastasis of various cancers, and it is an important biological process in which epidermal malignant cells acquire the ability to migrate and invade [12,13,14]. us, understanding the mechanism of miR-200b in regulating EMT is very important
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