The role of high mobility group AT-hook 1 in viral infections: Implications for cancer pathogenesis.

The crucial role of high mobility group AT-hook 1 (HMGA1) proteins in nuclear processes such as gene transcription, DNA replication, and chromatin remodeling is undeniable. Elevated levels of HMGA1 have been associated with unfavorable clinical outcomes and adverse differentiation status across various cancer types. HMGA1 regulates a diverse array of biological pathways, including tumor necrosis factor-alpha/nuclear factor-kappa B (TNF-α/NF-κB), epidermal growth factor receptor (EGFR), Hippo, Rat sarcoma/extracellular signal-regulated kinase (Ras/ERK), protein kinase B (Akt), wingless-related integration site/beta-catenin (Wnt/beta-catenin), and phosphoinositide 3-kinase/protein kinase B (PI3-K/Akt). While researchers have extensively investigated tumors in the reproductive, digestive, urinary, and hematopoietic systems, mounting evidence suggests that HMGA1 plays a critical role as a tumorigenic factor in tumors across all functional systems. Given its broad interaction network, HMGA1 is an attractive target for viral manipulation. Some viruses, including herpes simplex virus type 1, human herpesvirus 8, human papillomavirus, JC virus, hepatitis B virus, human immunodeficiency virus type 1, severe acute respiratory syndrome Coronavirus 2, and influenza viruses, utilize HMGA1 influence for infection. This interaction, particularly in oncogenesis, is crucial. Apart from the direct oncogenic effect of some of the mentioned viruses, the hit-and-run theory postulates that viruses can instigate cancer even before being completely eradicated from the host cell, implying a potentially greater impact of viruses on cancer development than previously assumed. This review explores the interplay between HMGA1, viruses, and host cellular machinery, aiming to contribute to a deeper understanding of viral-induced oncogenesis, paving the way for innovative strategies in cancer research and treatment.

The c.1243T>C mutation in the PROC gene is linked with inherited protein C deficiency and severe purpura fulminans.

Purpura fulminans is a severe coagulation disorder that often leads to death in neonates. Mutations in the protein C (PROC) gene can cause protein C deficiency, leading to this disorder. This study aimed to investigate a family with a history of coagulopathies, particularly those related to protein C deficiency. The primary objective was to identify any genetic mutations in the PROC gene responsible for the coagulopathies. The study focused on a male neonate with purpura fulminans who ultimately died at 2 months of age. The patient had low protein C activity levels (6%). The entire PROC gene of the patient and his family was analyzed using next-generation sequencing to identify any genetic mutations. Segregation analysis was conducted to determine if the mutation followed an autosomal dominant inheritance pattern. In silico analysis was also conducted to evaluate the pathogenicity of the identified mutation. Analysis revealed a novel homozygous c.1243T>G variant PROC gene. The mutation resulted in a Phe415Val substitution. The mutation was found in at least three generations of the family. Carrier family members had lower protein C activity levels than wild-type homozygotes. Additionally, the mutation may account for the observed reduction in protein C enzyme activity.

P53, CK20, and FGFR3 Overexpression is Associated with the Characteristics of Urothelial Cell Carcinoma of the Bladder

OBJECTIVES: The aim of this study was to investigate the association between the overexpression of tumor protein (P53), cytokeratin 20 (CK20), fibroblast growth factor receptor 3 (FGFR3), biomarkers and the grading, prognosis, heterogeneity, and relapse tendency of urothelial cell carcinomas (UCCs) of the bladder. METHODS: A cross-sectional study was conducted using 413 samples of Iranian patients diagnosed with UCC of the bladder. The tissue microarray technique was used to evaluate the patterns of tumor tissue. Two pathologists scored tissue staining using a semi-quantitative scoring system. RESULTS: The results showed that P53 was a predictor of a high-grade pattern (the area under the curve (AUC)=0.620) with a best cut-off value of 95.0 using the receiver operating characteristic (ROC) curve. CK20 was another predictor of a high-grade pattern (AUC=0.745) with a best cut-off value of 15. However, the overexpression of both biomarkers was not associated with a heterogeneous pattern and could not predict tumor-associated death or relapse. The heterogeneous (odds ratio (OR)=4.535, p-value=0.001) and non-papillary (OR= 6.363, p-value= 0.001) patterns were effective predictors of tumor recurrence among all baseline variables, including patient and tumor characteristics. FGFR3 was positive in all specimens and was not a valuable biomarker for differentiating patterns. None of the variables predicted tumor prognosis. CONCLUSION: The study findings indicate that the intensity and percentage of cell staining for P53 and CK20 in the UCC of the bladder can aid in differentiating the grading patterns. The tendency of tumor relapse can be predicted by demonstrating heterogeneous and non-papillary patterns.