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.
Oral cancer is a neoplastic disorder of the oral cavities, including the lips, tongue, buccal mucosa, and lower and upper gums. Oral cancer assessment entails a multistep process that requires deep ...knowledge of the molecular networks involved in its progression and development. Preventive measures including public awareness of risk factors and improving public behaviors are necessary, and screening techniques should be encouraged to enable early detection of malignant lesions. Herpes simplex virus (HSV), human papillomavirus (HPV), Epstein-Barr virus (EBV), and Kaposi sarcoma-associated herpesvirus (KSHV) are associated with other premalignant and carcinogenic conditions leading to oral cancer. Oncogenic viruses induce chromosomal rearrangements; activate signal transduction pathways via growth factor receptors, cytoplasmic protein kinases, and DNA binding transcription factors; modulate cell cycle proteins, and inhibit apoptotic pathways. In this review, we present an up-to-date overview on the use of nanomaterials for regulating viral proteins and oral cancer as well as the role of phytocompounds on oral cancer. The targets linking oncoviral proteins and oral carcinogenesis were also discussed.
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). To ensure its own survival and propagation, KSHV ...employs an extensive network of viral proteins to subvert the host immune system, resulting in lifelong latent infection. Modulation of cellular and systemic immune defenses allows KSHV to persist in the host, which may eventually lead to the progression of KSHV-associated cancers. Due to KSHV's reliance on modifying immune responses to efficiently infect its host, immunotherapy is an attractive option for treating KSHV-associated malignancies. In this review, we will focus on the mechanisms by which KSHV evades the immune system and the current immune-related clinical strategies to treat KSHV-associated disease.
The mitotic spindle assembly checkpoint (SAC) is an intricate cell signaling system that ensures the high fidelity and timely segregation of chromosomes during cell division. Mistakes in this process ...can lead to the loss, gain, or rearrangement of the genetic material. Gross chromosomal aberrations are usually lethal but can cause birth and development defects as well as cancer. Despite advances in the identification of SAC protein components, important details of the interactions underpinning chromosome segregation regulation remain to be established. This review discusses the current understanding of the function, structure, mode of regulation, and dynamics of the assembly and disassembly of SAC subcomplexes, which ultimately safeguard the accurate transmission of a stable genome to descendants. We also discuss how diverse oncoviruses take control of human cell division by exploiting the SAC and the potential of this signaling circuitry as a pool of drug targets to develop effective cancer therapies.
Gene editing, especially with clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9), has advanced gene function science. Gene editing's rapid advancement has ...increased its medical/clinical value. Due to its great specificity and efficiency, CRISPR/Cas9 can accurately and swiftly screen the whole genome. This simplifies disease-specific gene therapy. To study tumor origins, development, and metastasis, CRISPR/Cas9 can change genomes. In recent years, tumor treatment research has increasingly employed this method. CRISPR/Cas9 can treat cancer by removing genes or correcting mutations. Numerous preliminary tumor treatment studies have been conducted in relevant fields. CRISPR/Cas9 may treat gene-level tumors. CRISPR/Cas9-based personalized and targeted medicines may shape tumor treatment. This review examines CRISPR/Cas9 for tumor therapy research, which will be helpful in providing references for future studies on the pathogenesis of malignancy and its treatment.
The role of human oncoviruses in melanoma has been poorly investigated. The aim of this study was to investigate the association between oncoviruses and melanomas searching for human papillomavirus ...(HPV), Epstein Barr virus (EBV), and human herpesvirus 8DNA in melanoma specimens. Formalin‐fixed and paraffin‐embedded tissue specimens of cutaneous, mucosal, and ocular melanomas (OM) were selected from the Pathology Departments of the Galliera Hospital (Genoa) and the University Hospitals of Turin and Cagliari. Cutaneous and mucosal nevi have been collected as controls. The oncoviruses search has been performed with different polymerase chain reaction reagent kits. Fifty‐four melanomas (25 mucosal, 12 ocular, and 17 cutaneous) and 26 nevi (15 cutaneous and 11 mucosal) specimens were selected. The detection rate for one of the investigated oncoviruses was 17% in mucosal, 20% in ocular, and 0% in cutaneous melanomas (CMs). Despite the differences between groups seeming remarkable, there was no statistical significance (p > 0.5). Our data do not support a primary role of oncoviruses in melanoma carcinogenesis; however, the finding of HPV and EBV DNA in a considerable fraction of mucosal and OMs suggests that these viruses may act as cofactors in the development of extra‐CMs.
Oncogenic viruses are among the apparent causes of cancer-associated mortality. It was estimated that 12% to 15% of human malignancies are linked to oncoviruses. Although modernist strategies and ...traditional genetic studies have defined host-pathogen interactions of the oncoviruses, their host functions which are critical for the establishment of infection still remain mysterious. However, over the last few years, it has become clear that infections hijack and modify cellular pathways for their benefit. In this context, we constructed the virus-host protein interaction networks of seven oncoviruses (EBV, HBV, HCV, HTLV-1, HHV8, HPV16, and HPV18), and revealed cellular pathways hijacking as a result of oncogenic virus infection. Several signaling pathways/processes such as TGF-β signaling, cell cycle, retinoblastoma tumor suppressor protein, and androgen receptor signaling were mutually targeted by viruses to induce oncogenesis. Besides, cellular pathways specific to a certain virus were detected. By this study, we believe that we improve the understanding of the molecular pathogenesis of viral oncogenesis and provide information in setting new targets for treatment, prognosis, and diagnosis.
•TGF-β signaling is enriched by EBV, HCV, HTLV1, HHV8, HPV16/18 targeted proteins.•EBV, HTLV1, HHV8 and HPV16 host targets alter retinoblastoma tumor suppressor protein.•EGFR and p53 pathways are affected by HTLV1 and HPV16 infections.•Altered TNF-α signaling, Notch signaling and NF-KB signaling are observed in HCV infection.
Viral oncogenesis is a multistep process largely depending on the complex interplay between viruses and host factors. The oncoviruses are capable of subverting the cell signaling machinery and ...metabolic pathways and exploit them for infection, replication, and persistence. Several viral oncoproteins are able to functionally inactivate the tumor suppressor p53, causing deregulated expression of many genes orchestrated by p53, such as those involved in apoptosis, DNA stability, and cell proliferation. The Epstein⁻Barr virus (EBV) BZLF1, the high-risk human papillomavirus (HPV) E6, and the hepatitis C virus (HCV) NS5 proteins have shown to directly bind to and degrade p53. The hepatitis B virus (HBV) HBx and the human T cell lymphotropic virus-1 (HTLV-1) Tax proteins inhibit p53 activity through the modulation of p300/CBP nuclear factors, while the Kaposi's sarcoma herpesvirus (HHV8) LANA, vIRF-1 and vIRF-3 proteins have been shown to destabilize the oncosuppressor, causing a decrease in its levels in the infected cells. The large T antigen of the Merkel cell polyomavirus (MCPyV) does not bind to p53 but significantly reduces p53-dependent transcription. This review describes the main molecular mechanisms involved in the interaction between viral oncoproteins and p53-related pathways as well as in the development of therapeutic strategies targeting such interactions.
Some viruses are known to be associated with the onset of specific cancers. These microorganisms, oncogenic viruses or oncoviruses, can convert normal cells into cancer cells by modulating the ...central metabolic pathways or hampering genomic integrity mechanisms, consequently inhibiting the apoptotic machinery and/or enhancing cell proliferation. Seven oncogenic viruses are known to promote tumorigenesis in humans: human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), Epstein-Barr virus (EBV), human T-cell leukemia virus 1 (HTLV-1), Kaposi sarcoma-associated herpesvirus (KSHV), and Merkel cell polyomavirus (MCPyV). Recent research indicates that SARS-CoV-2 infection and COVID-19 progression may predispose recovered patients to cancer onset and accelerate cancer development. This hypothesis is based on the growing evidence regarding the ability of SARS-CoV-2 to modulate oncogenic pathways, promoting chronic low-grade inflammation and causing tissue damage. Herein, we summarize the main relationships known to date between virus infection and cancer, providing a summary of the proposed biochemical mechanisms behind the cellular transformation. Mechanistically, DNA viruses (such as HPV, HBV, EBV, and MCPyV) encode their virus oncogenes. In contrast, RNA viruses (like HCV, HTLV-1) may encode oncogenes or trigger host oncogenes through cis-/-trans activation leading to different types of cancer. As for SARS-CoV-2, its role as an oncogenic virus seems to occur through the inhibition of oncosuppressors or controlling the metabolic and autophagy pathways in the infected cells. However, these effects could be significant in particular scenarios like those linked to severe COVID-19 or long COVID. On the other hand, looking at the SARS-CoV-2─cancer relationship from an opposite perspective, oncolytic effects and anti-tumor immune response were triggered by SARS-CoV-2 infection in some cases. In summary, our work aims to recall comprehensive attention from the scientific community to elucidate the effects of SARS-CoV-2 and, more in general, β-coronavirus infection on cancer susceptibility for cancer prevention or supporting therapeutic approaches.
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