RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

Abstract

Nearly 7.5% of all human protein-coding genes have been assigned to the class of RNA-binding proteins (RBPs), and over the past decade, RBPs have been increasingly recognized as important regulators of molecular and cellular homeostasis. RBPs regulate the post-transcriptional processing of their target RNAs, i.e., alternative splicing, polyadenylation, stability and turnover, localization, or translation as well as editing and chemical modification, thereby tuning gene expression programs of diverse cellular processes such as cell survival and malignant spread. Importantly, metastases are the major cause of cancer-associated deaths in general, and particularly in oral cancers, which account for 2% of the global cancer mortality. However, the roles and architecture of RBPs and RBP-controlled expression networks during the diverse steps of the metastatic cascade are only incompletely understood. In this review, we will offer a brief overview about RBPs and their general contribution to post-transcriptional regulation of gene expression. Subsequently, we will highlight selected examples of RBPs that have been shown to play a role in oral cancer cell migration, invasion, and metastasis. Last but not least, we will present targeting strategies that have been developed to interfere with the function of some of these RBPs.

Keywords: DDX3; HNSCC; HuR; IGF2BP3; LIN28; METTL3; OSCC; RBP; oral cancer.

Figure 1

Functional hallmarks of RNA-binding proteins (RBPs). RBPs are important post-transcriptional regulators of gene expression. They are well-known to regulate RNA translation, splicing, transport, editing and chemical modification as well as turnover. Moreover, emerging functions of RBPs in co-translational protein complex assembly, protein localization and protein folding have been recently suggested. Hence, deregulated RBP activities can have broad effects on cellular homeostasis and are associated with several human diseases. Oral cancer-associated RBPs highlighted in this article have been assigned to relevant hallmark functionalities based on their established roles in human cancers as well as developmental processes.