Abstract
The present study was carried out to investigate the expression pattern, clinical significance and biological functions of microRNA-30d (miR-30d) in esophageal carcinogenesis. Quantitative real-time PCR was performed to detect the expression levels of miR-30d in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. Then, associations between miR-30d expression and various clinicopathological features of patients with ESCC were statistically evaluated. In addition, the effects of miR-30d on the migration and invasion of two human ESCC cell lines transfected with miRNA or co-transfected with miRNA mimics and the expression vector of its target gene were determined. The results revealed that the expression levels of miR-30d were markedly decreased in ESCC tissues and cell lines, comparing with the corresponding normal controls. Notably, reduced expression of miR-30d occurred more frequently in ESCC patients with positive lymph node metastasis, moderate-poor differentiation and advanced tumor-node-metastasis stage than those with negative features. Functionally, enforced expression of miR-30d was found to inhibit cell invasion and migration of the ESCC cell lines. Luciferase reporter assay identified enhancer of zeste homolog2 (EZH2) as a direct target gene of miR-30d. The expression level of EZH2 mRNA was negatively correlated with the expression of miR-30d in the ESCC tissues. Moreover, the inhibitory effect of miR-30d on ESCC cell motility was reversed by EZH2 overexpression. Collectively, these findings provide convincing evidence that decreased expression of miR-30d may be implicated in esophageal carcinogenesis and progression. We also confirmed miR-30d as a tumor-suppressor which may inhibit cancer cell motility by targeting EZH2, a potential therapeutic target for ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma represent two main histopathological subtypes of esophageal cancer, which is the eighth most common cancer and the sixth leading cause of cancer-related mortality worldwide, affecting men more than women [1]
The median value of miR-30d (1.21) expression levels in 60 ESCC tissues was used as a cut-off point to divide all 60 patients with ESCC into low miR-30d expression (n=32) and high miR-30d expression (n=28) groups
We demonstrated that the expression level of miR-30d in ESCC tissues was markedly lower than the level in adjacent non-cancerous esophageal mucosal tissues, which was similar with the observations observed using two human ESCC cell lines and one human normal esophageal cell line
Summary
Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma represent two main histopathological subtypes of esophageal cancer, which is the eighth most common cancer and the sixth leading cause of cancer-related mortality worldwide, affecting men more than women [1]. ESCC is characterized by its poor prognosis, with a 5-year survival rate less than 15% [2]. In Western countries, the incidence and the mortality rates of ESCC have steadily increased during the past few decades [3]. Despite advancement in radical esophagectomy and systemic chemoradiotherapy, the clinical outcome of ESCC patients is still very poor due to the high prevalence of cell proliferation and metastasis [4]. Most ESCC patients are often diagnosed at an advanced stage due to the absence of apparent symptoms and lack of early detection methods [5]. It is of great clinical significance to discover and identify tumor-specific molecular biomarkers for the early detection and effective treatment, and subsequently for the better understanding of the underlying biological mechanisms of ESCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
