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.

Oral squamous cell carcinoma (OSCC) is the 10th most frequent human malignancy and is thus a global burden. Despite some progress in diagnosis and therapy, patients’ overall survival rate, between 40 and 55%, has stagnated over the last four decades. Since the tumor node metastasis (TNM) system is not precise enough to predict the disease outcome, additive factors for diagnosis, prognosis, prediction and therapy resistance are urgently needed for OSCC. One promising candidate is the hypoxia inducible factor-1 (HIF-1), which functions as an early regulator of tumor aggressiveness and is a key promoter of energy adaptation. Other parameters comprise the composition of the tumor microenvironment, which determines the availability of nutrients and oxygen. In our opinion, these general processes are linked in the pathogenesis of OSCC. Based on this assumption, the review will summarize the major features of the HIF system-induced activities, its target proteins and related pathways of nutrient utilization and metabolism that are essential for the initiation, progression and therapeutic stratification of OSCC.

Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance due to an increased knowledge of its underlying molecular mechanisms and its modulation by the tumor microenvironment and immune cell repertoire. In this study, the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 pathologically classified human papilloma virus (HPV)-negative OSCC lesions and correlated to the intra-tumoral immune cell response, IFN-γ signaling and to the patient’s outcome. A heterogeneous but predominantly lower constitutive protein expression of HLA-I APM components was found in OSCC sections when compared to non-neoplastic cells. Tumoral HLA-I APM component expression was further categorized into the three major phenotypes HLA-I^high/APM^high, HLA-I^low/APM^low and HLA-I^{discordant high/low}/APM^high. In the HLA-I^high/APM^high group, the highest frequency of intra-tumoral CD8⁺ T cells and lowest number of CD8⁺ T cells close to FoxP3⁺ cells were found. Patients within this group presented the most unfavorable survival, which was significantly evident in stage T2 tumors. Despite a correlation with the number of intra-tumoral CD8⁺ T cells, tumoral JAK1 expression as a surrogate marker for IFN-γ signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren’s syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue.

Orbital floor fractures represent a common fracture type of the midface and are standardly diagnosed clinically as well as radiologically using linear measurement methods. The aim of this study was to evaluate the accuracy of diagnostic measurements of isolated orbital floor fractures based on two-dimensional (2D) and three-dimensional (3D) measurement techniques. A cohort of 177 patients was retrospectively and multi-centrically evaluated after surgical treatment of an orbital floor fracture between 2010 and 2020. In addition to 2D and 3D measurements of the fracture area, further fracture-related parameters were investigated. Calculated fracture areas using the 2D measurement technique revealed an average area of 287.59 mm², whereas the 3D measurement showed fracture areas with a significantly larger average value of 374.16 mm² (p < 0.001). On average, the 3D measurements were 1.53-fold larger compared to the 2D measurements. This was observed in 145 patients, whereas only 32 patients showed smaller values in the 3D-based approach. However, the process duration of the 3D measurement took approximately twice as long as the 2D-based procedure. Nonetheless, 3D-based measurement of orbital floor defects provides a more accurate estimation of the fracture area than the 2D-based procedure and can be helpful in determining the indication and planning the surgical procedure.

Orbital floor fractures (OFFs) are common injuries of the midface and may result in long-term complications. The aim of this study was to compare two restoration materials, PDS foils and titanium meshes, with regards to (1) clinical outcome and (2) reduction in orbital volume. The monocentric discovery cohort was analyzed retrospectively and included 476 patients with OFFs treated between 2010 and 2020. A subcohort of 104 patients (study cohort) with isolated OFFs and available high-resolution imaging material was used for volume measurements. Postoperative complications were not significantly different between patients treated with different restoration materials. Prevalence of revision surgery was significantly higher in patients treated with thick PDS foils (25 mm). OFFs treated with PDS foils and titanium meshes showed a significant reduction in orbital volume (p = 0.0422 and p = 0.0056, respectively), however, this volume decrease was significantly less pronounced in patients treated with PDS foils alone (p = 0.0134). Restoration using PDS foil in an isolated OFF reduces the orbital volume to a lesser extent than titanium mesh. Class III patients according to the classification of Jaquiéry with a missing bony ledge medial to the infraorbital fissure particularly benefit from restoration with PDS foils due to a lower reduction in the orbital volume. Regarding short- and long-term postoperative complications, a PDS foil thickness of 0.15 mm appears equivalent to titanium mesh in the treatment of OFFs.