Abstract
MiRNA-126 (miR-126) has been shown to be involved in various malignancies as well as other biological processes. However, currently, its role in esophageal squamous cell carcinoma (ESCC) is not well understood. The present study is focused on the mechanisms that underlie the effect of miR-126 on cell survival and death (apoptosis and autophagy) in ESCC cells. MiR-126 expression was found to be enhanced in ESCC cells and tissues. Downregulation of miR-126 suppressed cell survival, and TUNEL staining indicated that miR-126 inhibition promoted ESCC cell death. In addition, the production of LC3B and p62 proteins, two autophagy signals, was reduced following miR-126 inhibition. A dual luciferase reporter assay demonstrated that the STAT3 3’-UTR is a direct target of miR-126. Furthermore, STAT3 knock-down rescued the effects on autophagy and apoptosis caused by miR-126 inhibition in ESCC cells. The results of this study may provide some insight into the molecular and biological mechanisms underlying ESCC generation and contribute to the development of novel therapeutic approaches for ESCC.
Highlights
Esophageal cancer (EC) is a fatal disorder typified by a poor clinical outcome owing, in part, to the fact that many patients with EC receive their diagnosis during the late stages of the illness [1, 2]
The results showed that miR-126 expression was enriched in the human esophageal squamous cell carcinoma (ESCC) specimens, indicating a higher level of miR-126 in ESCC tumors than in the surrounding normal esophageal tissues (Figure 1B)
Tumorigenesis is a synergistic process involving the activation of multiple oncogenes, tumor inhibitor genes, and epigenetic alterations, all of which lead to tumor formation
Summary
Esophageal cancer (EC) is a fatal disorder typified by a poor clinical outcome owing, in part, to the fact that many patients with EC receive their diagnosis during the late stages of the illness [1, 2]. Remarkable progress has been made in diagnostic methods and adjuvant chemotherapy, the five-year survival rate of patients with EC remains below 30% [3]. Previous studies have indicated that complex epigenetic and genetic changes may result in the progression of esophageal squamous cell carcinoma (ESCC) [4, 5]. A proper understanding of the mechanisms underlying such changes is currently lacking. Current evidence suggests that miRNAs may critically influence various biological processes, including cell death. MiR-34a is suppressed in malignancies as well as in multiple cellular processes such as cell proliferation, differentiation, and death [7,8,9]
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