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.

Studies on carcinogenesis continue to provide new information about different disease-related processes. Among others, much research has focused on the involvement of cancer stem cells (CSCs) in tumor initiation and progression. Studying the similarities and differences between CSCs and physiological stem cells (SCs) allows for a better understanding of cancer biology. Recently, it was shown that stem cell identity is partially governed by the Krϋppel-associated box domain zinc finger proteins (KRAB-ZFPs), the biggest family of transcription regulators. Several KRAB-ZFP factors exert a known effect in tumor cells, acting as tumor suppressor genes (TSGs) or oncogenes, yet their role in CSCs is still poorly characterized. Here, we review recent studies regarding the influence of KRAB-ZFPs and their cofactor protein TRIM28 on CSCs phenotype, stemness features, migration and invasion potential, metastasis, and expression of parental markers.

Zwilch kinetochore protein (ZWILCH) plays a key role in proper cell proliferation. The upregulation of the ZWILCH gene was observed in many types of cancers, but the association of ZWILCH with adrenocortical carcinoma (ACC) was not investigated so far. The main aim of the presented study was to verify if the enhanced level of the ZWILCH gene can be used as a diagnostic marker for ACC development and progression, as well as a predictor of survival time for ACC patients. The performed analyses included investigation of the ZWILCH expression profile in tumors with publicly available TCGA (The Cancer Genome Atlas) datasets and transcriptomic data from the Gene Expression Omnibus (GEO) database, as well as, in human biological samples of normal adrenal, adrenocortical carcinoma and in commercially available tissue microarrays. The findings demonstrate statistically significant higher ZWILCH gene expression in ACC tissue in comparison with normal adrenal glands. Furthermore, there is a strong correlation between ZWILCH upregulation and tumor mitotic rate and the probability of patient survival. The enhanced ZWILCH level is also connected with the activation of genes involved in cell proliferation and the inhibition of genes related to the immune system. This work contributes to a better understanding of the role of ZWILCH as an ACC biomarker and diagnostic tool.

Asthma is the most frequent chronic disease in children. One of the most replicated genetic findings in childhood asthma is the ORMDL3 gene confirmed in several GWA studies in several pediatric pop...

Despite the ongoing progress in diagnosis and treatments, cancer remains a threat to more than one-third of the human population. The emerging data indicate that many Krüppel-associated box zinc finger proteins (KRAB-ZNF) belonging to a large gene family may be involved in carcinogenesis. Our previous study identified Zinc Finger Protein 714 (ZNF714), a KRAB-ZNF gene of unknown function, as being commonly overexpressed in many tumors, pointing to its hypothetical oncogenic role. Here, we harnessed The Cancer Genome Atlas (TCGA)-centered databases and performed functional studies with transcriptomic and methylomic profiling to explore ZNF714 function in cancer. Our pan-cancer analyses confirmed frequent ZNF714 overexpression in multiple tumors, possibly due to regional amplification, promoter hypomethylation, and Nuclear Transcription Factor Y Subunit Beta (NFYB) signaling. We also showed that ZNF714 expression correlates with tumor immunosuppressive features. The in vitro studies indicated that ZNF714 expression positively associates with proliferation, migration, and invasion. The transcriptomic analysis of ZNF714 knocked-down cells demonstrated deregulation of cell adhesion, migration, proliferation, apoptosis, and differentiation. Importantly, we provided evidence that ZNF714 negatively regulates the expression of several known TSGs indirectly via promoter methylation. However, as ZNF714 did not show nuclear localization in our research model, the regulatory mechanisms exerted by ZNF714 require further investigation. In conclusion, our results reveal, for the first time, that ZNF714 may support pro-oncogenic features in lung cancer cells.

Adrenal tumors, such as adrenocortical carcinoma (ACC), adrenocortical adenoma (ACA), and pheochromocytoma (PCC) are complex diseases with unclear causes and treatments. Mitochondria and mitochondrial-derived peptides (MDPs) are crucial for cancer cell survival. The primary aim of this study was to analyze samples from different adrenal diseases, adrenocortical carcinoma, adrenocortical adenoma, and pheochromocytoma, and compare them with normal adrenal tissue to determine whether the expression levels of the mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) gene and protein vary between different types of adrenal tumors compared to healthy controls using qPCR, ELISA, and IHC methods. Results showed decreased MOTS-c mRNA expression in all adrenal tumors compared to controls, while serum MOTS-c protein levels increased in ACA and PCC but not in ACC. The local distribution of MOTS-c protein in adrenal tissue was reduced in all tumors. Notably, MOTS-c protein expression declined with ACC progression (stages III and IV) but was unrelated to patient age or sex. Tumor size and testosterone levels positively correlated with MOTS-c mRNA but negatively with serum MOTS-c protein. Additionally, serum MOTS-c protein correlated positively with glucose, total cholesterol, HDL, LDL, and SHGB levels. These findings suggest disrupted expression of MOTS-c in the spectrum of adrenal diseases, which might be caused by mechanisms involving increased mitochondrial dysfunction and structural changes in the tissue associated with disease progression. This study provides a detailed examination of MOTS-c mRNA and protein in adrenal tumors, indicating the potential role of MDPs in tumor biology and progression.