Role of microRNA-138 as a potential tumor suppressor in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive life-threatening disease associated with high mortality rates. While efforts have been made to explore the molecular mechanisms that contribute to the initiation and progression of HNSCC, most studies focus on protein-coding genes. Understanding of the genomic aberrations associated with noncoding genes (such as microRNAs) and their effects on HNSCC is still relatively limited. Recent evidence suggests that deregulation of microRNA genes (such as downregulation of miR-138) plays an important role in HNSCC. While deregulation of miR-138 has been frequently observed in HNSCC and other cancer types, the precise roles of miR-138 in tumorigenesis remain elusive. Recent bioinformatics analyses and functional studies using in vitro and in vivo systems have identified a number of functional targets for miR-138. These include genes that participate in essential biological processes that are highly relevant to the initiation and progression of HNSCC, including cell migration, epithelial to mesenchymal transition, cell cycle progression, DNA damage response and repair, senescence, and differentiation. However, the biological systems, study design, and data interpretation from these studies are highly variable, which hinder our understanding of the role of miR-138 in tumorigenesis at molecular level. In this review, we will first introduce the significance of microRNA deregulation in HNSCC. We will then provide a comprehensive review and integrative analysis of the existing studies on miR-138, and aim to define its molecular mechanisms that contribute to the initiation and progression of HNSCC.