Content area
Full Text
Introduction
Esophageal cancer (EC) is the most common gastrointestinal tumor worldwide, with the highest incidence and mortality rates observed in China, where most cases are esophageal squamous cell carcinoma (ESCC) (1), and as the fourth cause of cancer death, the 5-year survival rate remains at 15–40% after current treatments (2–4). Indeed, the main causes of poor prognosis for ESCC patients are local invasion and lymph node and distant metastasis; thus, early detection is a key factor in increasing survivability (3), although the lack of effective and specificity markers still plagues the diagnosis. Of note, since carcinogenesis is a multi-step process, the diagnostic indices, such as epithelial mesenchymal transition (EMT), invasion, metastases, and recurrence, should dynamically change with the occurrence and development of tumors (5).
For squamous neoplasms, such as ESCCs, EMT is a crucial process, in which cancer cells lose polarity and reduce adhesion, contributing to migration to and invasion of surrounding issues (6). Therefore, discovering the mechanism and key factors that control EMT in tumors would provide strategies to solve the above dilemma. Recent data have demonstrated that microRNAs (miRNAs) as non-coding small RNAs not only exist widely in organisms, but also govern the expression of different genes by binding to the 3′-untranslated region of target genes and participating in a series of important processes, including differentiation, proliferation, apoptosis and EMT (7–9). However, study results are conflicting, and microRNAs play roles as tumor-suppressors or carcinogenic factors in various human malignancies (10). Studies have shown that miRNA-let-7 as a tumor suppressor, apparently has low expression in many tumor types, such as head and neck, gastric, lung, ovarian and esophageal cancers (11–16). Among the let-7 family, let-7a, have been implicated in the inhibition of EMT in nasopharyngeal, hepatocellular and rectal carcinoma, and breast cancer (17–20). Specifically, as a highly conserved RNA-binding protein, Lin28, which negatively regulates the maturation of let-7 by binding to the terminal loop of its precursor, has also been positively correlated with the cancer aggressiveness and poor prognosis of EC patients (12,16,17). Therefore, it is worth considering whether the changes of let-7a have a potential indicative effect of EMT, even metastasis for ESCC.
At this stage, the occurrence of EMT involves multiple signal transduction pathways, such as Notch, TNF-α, TGF-β, Wnt/β-catenin and others...