Roles of microRNAs in tumorigenesis and metastasis of esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancer that is prevalent in Eastern Asia. Despite recent advances in therapy, the outcome of ESCC patients is still dismal. MicroRNAs (miRNAs) are non-coding RNAs which can negatively modulate gene expression at the post-transcriptional level. The involvement and roles of miRNAs have become one of the hot topics of cancer research in recent years. In ESCC, genetic variations within miRNA coding genes were found to have distinct epidemiological significance in different populations. Dysregulated expression of several miRNAs was reported to be associated with therapeutic response. Functionally, miRNAs can act either in an oncogenic or a tumor-suppressive manner during tumorigenesis of ESCC by interrupting signaling pathways associated with cell proliferation, metabolism, cancer stemness, and resistance to chemo- or radiotherapy. Moreover, miRNAs modulate metastasis of ESCC by targeting genes that regulate cytoskeleton dynamics, extracellular matrix remodeling, epithelial-mesenchymal transition, and tumor microenvironment. Most importantly, mounting evidence suggests that inhibiting oncogenic miRNAs or restoring the loss of tumor-suppressive miRNAs has therapeutic potential in the treatment of ESCC. Here, we review and discuss recent studies on the significance, biological functions, and therapeutic potential of miRNAs in tumorigenesis and metastasis of ESCC.

Keywords: Dysregulation; Esophageal squamous cell carcinoma; Metastasis; MicroRNAs; Therapeutic potential; Tumorigenesis.

Figure 1

Multiple roles of miRNAs during development of esophageal squamous cell carcinoma. This figure summarizes the targets and regulatory functions of miRNAs in multiple biological processes during esophageal squamous cell carcinoma (ESCC) development. MicroRNAs inhibit or promote tumorigenesis and recurrence of ESCC by modulating cell proliferation, metabolism, cancer stemness, and resistance to chemo- or radiotherapy. They also regulate metastasis by targeting functional molecules involved in epithelial-mesenchymal transformation, remodeling of the cytoskeleton, extracellular matrix, and tumor microenvironment. Oncogenic miRNAs and target genes are marked in orange. PLCE1: Phospholipase C epsilon 1; VEGF: Vascular endothelial growth factor.