Head and neck squamous cell carcinoma is one of the most common and fatal cancers worldwide. Even a multimodal approach consisting of standard chemo- and radiotherapy along with surgical resection is only effective in approximately 50% of the cases. The rest of the patients develop a relapse of the disease and acquire resistance to treatment. Especially this group of individuals needs novel, personalized, targeted therapy. The first step to discovering such solutions is to investigate the tumor microenvironment, thus understanding the role and mechanism of the function of coding and non-coding sequences of the human genome. In recent years, RNA molecules gained great interest when the complex character of their impact on our biology allowed them to come out of the shadows of the “junk DNA” label. Furthermore, long non-coding RNAs (lncRNA), specifically the intergenic subgroup (lincRNA), are one of the most aberrantly expressed in several malignancies, which makes them particularly promising future diagnostic biomarkers and therapeutic targets. This review contains characteristics of known and validated lincRNAs in HNSCC, such as XIST, MALAT, HOTAIR, HOTTIP, lincRNA-p21, LINC02487, LINC02195, LINC00668, LINC00519, LINC00511, LINC00460, LINC00312, and LINC00052, with a description of their prognostic abilities. Even though much work remains to be done, lincRNAs are important factors in cancer biology that will become valuable biomarkers of tumor stage, outcome prognosis, and contribution to personalized medicine.

Pseudogenes were once considered as “junk DNA”, due to loss of their functions as a result of the accumulation of mutations, such as frameshift and presence of premature stop-codons and relocation of genes to inactive heterochromatin regions of the genome. Pseudogenes are divided into two large groups, processed and unprocessed, according to their primary structure and origin. Only 10% of all pseudogenes are transcribed into RNAs and participate in the regulation of parental gene expression at both transcriptional and translational levels through senseRNA (sRNA) and antisense RNA (asRNA). In this review, about 150 pseudogenes in the different types of cancers were analyzed. Part of these pseudogenes seem to be useful in molecular diagnostics and can be detected in various types of biological material including tissue as well as biological fluids (liquid biopsy) using different detection methods. The number of pseudogenes, as well as their function in the human genome, is still unknown. However, thanks to the development of various technologies and bioinformatic tools, it was revealed so far that pseudogenes are involved in the development and progression of certain diseases, especially in cancer.

Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers. Most cancer cases originate from alcohol and tobacco consumption. However, studies have demonstrated that human papillomavirus (HPV) infection, particularly HPV-16, may also significantly influence disease progression. The KRAB-ZNF family of genes is involved in epigenetic suppression, and its involvement in carcinogenesis is the subject of extensive studies. The available literature data demonstrate that they may play different roles, both as tumor suppressors and oncogenes. In this study, six ZNF genes, ZFP28, ZNF132, ZNF418, ZNF426, ZNF540, and ZNF880, were tested using several in silico approaches based on the TCGA and GEO datasets. Our analyses indicate that the expression of the analyzed ZNFs was significantly downregulated in tumor tissues and depended on tumor localization. The expression levels of ZNFs differed between HPV-positive vs. HPV-negative patients depending on the clinical-pathological parameters. More specifically, the patients with higher levels of ZNF418 and ZNF540 showed better survival rates than those with a lower expression. In addition, the level of ZNF540 expression in HPV-positive (HPV(+)) patients was higher than in HPV-negative (HPV(−)) patients (p < 0.0001) and was associated with better overall survival (OS). In conclusion, we demonstrate that ZNF540 expression highly correlates with HPV infection, which renders ZNF540 a potential biomarker for HNSCC prognosis and treatment.

Head and neck squamous cell carcinoma is one of the most common and fatal cancers worldwide. Lack of appropriate preventive screening tests, late detection, and high heterogeneity of these tumors are the main reasons for the unsatisfactory effects of therapy and, consequently, unfavorable outcomes for patients. An opportunity to improve the quality of diagnostics and treatment of this group of cancers are microRNAs (miRNAs) — molecules with a great potential both as biomarkers and therapeutic targets. This review aims to present the characteristics of these short non-coding RNAs (ncRNAs) and summarize the current reports on their use in oncology focused on medical strategies tailored to patients’ needs. Head and neck squamous cell carcinoma is one of the most common and fatal cancers worldwide. Lack of appropriate preventive screening tests, late detection, and high heterogeneity of these tumors are the main reasons for the unsatisfactory effects of therapy and, consequently, unfavorable outcomes for patients. An opportunity to improve the quality of diagnostics and treatment of this group of cancers are microRNAs (miRNAs) — molecules with a great potential both as biomarkers and therapeutic targets. This review aims to present the characteristics of these short non-coding RNAs (ncRNAs) and summarize the current reports on their use in oncology focused on medical strategies tailored to patients’ needs.

Long non-coding RNAs have proven to be important molecules in carcinogenesis. Due to little knowledge about them, the molecular mechanisms of tumorigenesis are still being explored. The aim of this work was to study the effect of ionizing radiation on the expression of lncRNAs in head and neck squamous cell carcinoma (HNSCC) in patients responding and non-responding to radiotherapy. The experimental model was created using a group of patients with response (RG, n = 75) and no response (NRG, n = 75) to radiotherapy based on the cancer genome atlas (TCGA) data. Using the in silico model, statistically significant lncRNAs were defined and further validated on six HNSCC cell lines irradiated at three different doses. Based on the TCGA model, C10orf55, C3orf35, C5orf38, CASC2, MEG3, MYCNOS, SFTA1P, SNHG3, and TMEM105, with the altered expression between the RG and NRG were observed. Analysis of pathways and immune profile indicated that these lncRNAs were associated with changes in processes, such as epithelial-to-mesenchymal transition, regulation of spindle division, and the p53 pathway, and differences in immune cells score and lymphocyte infiltration signature score. However, only C10orf55, CASC2, and SFTA1P presented statistically altered expression after irradiation in the in vitro model. In conclusion, the expression of lncRNAs is affected by ionization radiation in HNSCC, and these lncRNAs are associated with pathways, which are important for radiation response and immune response. Potentially presented lncRNAs could be used as biomarkers for personalized radiotherapy in the future. However, these results need to be verified based on an in vitro experimental model to show a direct net of interactions.

Long non-coding RNAs (lncRNAs) consist of at least 200 nucleotides. Although these molecules do not code proteins, they carry many regulatory functions in normal cells, as well as in cancer cells. For instance, many of these molecules have been previously correlated with tumorigenesis of different cancers and their reaction to various stress factors, such as radiotherapy, chemotherapy, or reactive oxygen species (ROS). The lncRNAs are associated not only with dysregulation in cancers after applied treatment but also with beneficial effects that may be achieved by modulating their expression, often significantly enhancing the patients’ outcomes. A multitude of these molecules was previously considered as potential biomarkers of tumor development, progression, or cells’ response to radio- or chemotherapy. Irradiation, which is often used in treating numerous cancer types, is not always sufficient due to cells gaining resistance in multiple ways. In this review, studies considering lncRNAs and their reaction to radiotherapy were examined. These molecules were divided regarding their role in specific processes strictly related to irradiation, and their influence on this type of treatment was explained, showing how vast an impact they have on IR-supported combat with the disease. This review aims to shed some light on potential future lncRNA-based biomarkers and therapeutic targets.