Krüppel-associated box zinc finger proteins (KRAB-ZFPs) constitute the largest family of transcriptional factors exerting co-repressor functions in mammalian cells. In general, KRAB-ZFPs have a dual structure. They may bind to specific DNA sequences via zinc finger motifs and recruit a repressive complex through the KRAB domain. Such a complex mediates histone deacetylation, trimethylation of histone 3 at lysine 9 (H3K9me3), and subsequent heterochromatization. Nevertheless, apart from their repressive role, KRAB-ZFPs may also co-activate gene transcription, likely through interaction with other factors implicated in transcriptional control. KRAB-ZFPs play essential roles in various biological processes, including development, imprinting, retroelement silencing, and carcinogenesis. Cancer cells possess multiple genomic, epigenomic, and transcriptomic aberrations. A growing number of data indicates that the expression of many KRAB-ZFPs is altered in several tumor types, in which they may act as oncogenes or tumor suppressors. Hereby, we review the available literature describing the oncogenic and suppressive roles of various KRAB-ZFPs in cancer. We focused on their association with the clinicopathological features and treatment response, as well as their influence on the cancer cell phenotype. Moreover, we summarized the identified upstream and downstream molecular mechanisms that may govern the functioning of KRAB-ZFPs in a cancer setting.

YRNAs are a type of short, noncoding RNAs. A total of four different transcripts can be distinguished, which are YRNA1, YRNA3, YRNA4 and YRNA5. All YRNAs are relatively small, made up of about 100 nucleotides each. YRNAs are characterized by a stem-loop structure and each part of that structure carries a different function. YRNAs are transcribed in the nucleus by RNA polymerase III. Then, the YRNA molecule is bound to the polyuridine tail of the La protein responsible for both its nuclear retention and protection from degradation. They also bind to the Ro60 protein, making the molecule more stable. In turn, YRNA-derived small RNAs (YsRNAs) are a class of YRNAs produced in apoptotic cells as a result of YRNA degradation. This process is performed by caspase-3-dependent pathways that form two groups of YsRNAs, with lengths of either approximately 24 or 31 nucleotides. From all four YRNA transcripts, 75 well-described pseudogenes are generated as a result of the mutation. However, available data indicates the formation of up to 1000 pseudogenes. YRNAs and YRNA-derived small RNAs may play a role in carcinogenesis due to their altered expression in cancers and influence on cell proliferation and inflammation. Nevertheless, our knowledge is still limited, and more research is required. The main aim of this review is to describe the current state of knowledge about YRNAs, their function and contribution to carcinogenesis, as well as their potential role in cancer diagnostics. To confirm the promising potential of YRNAs and YRNA-derived fragments as biomarkers, their significant role in several tumor types was taken into consideration.

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.

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a disorder caused by an autosomal dominant heterozygous germline mutation in one of the DNA mismatch repair (MMR) genes. Individuals with LS are at an increased risk of developing colorectal and extracolonic cancers, such as endometrial, small bowel, or ovarian. In this review, the mutations involved with LS and their diagnostic methods are described and compared, as are their current uses in clinical decision making. Nowadays, LS diagnosis is based on a review of family medical history, and when necessary, microsatellite instability (MSI) or/and immunohistochemistry (IHC) analyses should be performed. In the case of a lack of MMR protein expression (dMMR) or MSI-H (MSI-High) detection in tumor tissue, molecular genetic testing can be undertaken. More and more genetic testing for LS is based mainly on next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA), which provide better and quicker information about the molecular profile of patients as well as individuals at risk. Testing based on these two methods should be the standard and commonly used. The identification of individuals with mutations provides opportunities for the detection of cancer at an early stage as well as the introduction of proper, more effective treatment, which will result in increased patient survival and reduced costs of medical care.

Numerous studies have shown that human papillomavirus (HPV) infection is one of the important risk factors for head and neck squamous cell carcinoma (HNSCC) progression and affects the expression of multiple genes, which might serve as new biomarkers. This study examines the effects of HPV infection on long non-coding RNA (lncRNA) expression and the immune system, particularly PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). The Cancer Genome Atlas (TCGA) expression data for lncRNA genes and clinical data were analyzed by GraphPad Prism 5/7. The expressions of PRINS, CDKN2B-AS1, TTTY14, TTTY15, MEG3, and H19 were significantly different in HPV-positive and HPV-negative patients. HPV-positive patients with high PRINS expression demonstrated significantly better overall survival (OS) and disease-free survival (DFS). HPV-positive patients with high PRINS expression showed changes in gene expression associated with immune and antiviral responses. A majority of HPV-positive patients with high PRINS expression demonstrated a high number of immune cells within tumors. PRINS expression was significantly associated with HPV-infection HNSCC tumors. Validation of these results using data set from Gene Expression Omnibus (GEO) indicated that PRINS is upregulated in HPV active infections and in “atypical 1 (IR)” HNSCC clusters, negatively influencing patients’ overall survival. Patients with high PRINS expression display different immunological profiles than those with low expression levels. For instance, they have active HPV infection status or are clustered in the “atypical 1 (IR)” subtype of HNSCC which influences both viral infection and patients’ survival. It is likely that PRINS could be used as a potential biomarker for HNSCC patients, but its role is dual. On the one hand, it stimulates patients’ immune response, while on the other it can be favorable in virus replication.

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.