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.

miR-154 Influences HNSCC Development and Progression through Regulation of the Epithelial-to-Mesenchymal Transition Process and Could Be Used as a Potential Biomarker

“…Another identified target within this study was ESRP1. ESRP1 and ESRP2 play an important role in alternative splicing, and their expression is reduced during the EMT process [ 89 ]. It has been indicated that both were upregulated in dysplastic samples of OSCC, but their reduction was probably restricted in the cells that had a motile phenotype acquired during cancer invasion [ 90 ].…”

Musashi–1—A Stemness RBP for Cancer Therapy?

“…RNA–binding proteins (RBPs) control all aspects of post–transcriptional gene expression, including RNA splicing and editing, transport and localization, mRNA turnover and translation as well as miRNA biogenesis [ 1 , 2 ]. Therefore, they play essential roles during development, but also serve essential roles in tumor biology by modulating essentially all hallmarks of cancer [ 2 , 3 ]. De–regulation of RBPs is associated with a variety of human malignancies, including solid cancers, and targeting their expression or functions provides alternative strategies for cancer therapy [ 4 , 5 , 6 ].…”

Interaction Between LncRNA and UPF1 in Tumors

“…RBPs have been recognized as key regulators of transcription and post-transcriptional processing ( Janakiraman et al, 2018 ; Xu et al, 2019 ). A large body of work has shown that many RBPs have impacts on tumorigenesis and cancer cell survival ( Gao et al, 2020 ; Schultz et al, 2020 ; Weiße et al, 2020 ). Recent research into ncRNAs has revealed the existence of complex RBP-ncRNA interactions ( Jonas et al, 2020 ).…”