Abstract
Accumulating evidence has established that long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is a tumor regulator in many cancers. Here, we aimed to investigate the possible function of lncRNA PVT1 in esophageal carcinoma (EC) via targeting of microRNA‐145 (miR‐145). Initially, microarray‐based gene expression profiling of EC was employed to identify differentially expressed genes. Moreover, the expression of lncRNA PVT1 was examined and the cell line presenting with the highest level of lncRNA PVT1 expression was selected for subsequent experiments. We then proceeded to examine interaction among lncRNA PVT1, FSCN1, and miR‐145. The effect of lncRNA PVT1 on viability, migration, invasion, apoptosis, and tumorigenesis of transfected cells was examined with gain‐of‐function and loss‐of‐function experiments. We observed that lncRNA PVT1 was robustly induced in EC. lncRNA PVT1 could bind to miR‐145 and regulate its expression, and FSCN1 is a target gene of miR‐145. Overexpression of miR‐145 or silencing of lncRNA PVT1 was revealed to suppress cell viability, migration, and invasion abilities, while also stimulating cell apoptosis. Furthermore, our in vivo results showed that overexpression of miR‐145 or silencing of lncRNA PVT1 resulted in decreased tumor growth in nude mice. In conclusion, our research reveals that down‐regulation of lncRNA PVT1 could potentially promote expression of miR‐145 to repress cell migration and invasion, and promote cell apoptosis through the inhibition of FSCN1. This highlights the potential of lncRNA PVT1 as a therapeutic target for EC treatment.
Highlights
Esophageal carcinoma (EC) serves as a common malignant gastrointestinal tumor
esophageal carcinoma (EC) is one of the most common types of cancer accompanied by poor prognosis, and the poor outcomes in EC patients are related to diagnosis at advanced stages and the tendency for metastases (Liu et al, 2018b). Long noncoding RNAs (lncRNAs) and miRNAs have been revealed to have the potential to function in the initiation and progression of EC (Pan et al, 2016; Qi et al, 2017)
The initial results from western blot analysis and reverse transcription–quantitative polymerase chain reaction (RT-qPCR) showed that miR-145 was poorly expressed, but lncRNA plasmacytoma variant translocation 1 (PVT1) and FSCN1 were highly expressed in EC. miR-145 was down-regulated in many types of human cancer, including gastrointestinal tract (Chen et al, 2010), lung cancer (Ling et al, 2015), and gallbladder cancer (Letelier et al, 2014)
Summary
Esophageal carcinoma (EC) serves as a common malignant gastrointestinal tumor. It is one of the main causes of tumor-related mortality (Shiba et al, 2018). The common risk factors responsible for EC include smoking, drinking, and high body mass index.
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