Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.

Protein SUMOylation, a post-translational modification, intricately regulates diverse biological processes including gene expression, cell cycle progression, signaling pathway transduction, DNA damage response, and RNA metabolism. This modification contributes to the acquisition of tumorigenicity and the maintenance of cancer hallmarks. In malignancies, protein SUMOylation is triggered by various cellular stresses, promoting tumor initiation and progression. This augmentation is orchestrated through its specific regulatory mechanisms and characteristic biological functions. This review focuses on elucidating the fundamental regulatory mechanisms and pathological functions of the SUMO pathway in tumor pathogenesis and malignant evolution, with particular emphasis on the tumorigenic potential of SUMOylation. Furthermore, we underscore the potential therapeutic benefits of targeting the SUMO pathway, paving the way for innovative anti-tumor strategies by perturbing this dynamic and reversible modifying process.

Concentration quenching inhibition and fluorescence enhancement in Eu3+-doped molybdate red phosphors with two-phase mixing.

Red phosphor plays a crucial role in improving the quality of white light illumination and backlight displays. However, significant challenges remain to enhance red emission intensity in different matrix materials. Herein, a class of two-phase mixing red phosphors of NaIn1-x(MoO4)2:xEu3+ (NIMO:xEu3+) has been successfully prepared by the traditional high-temperature solid-state reaction method. The coordination environment, phase structure, excitation and emission spectra, fluorescence kinetics, and temperature-dependent luminescence properties of the system have been studied comprehensively. It is worth mentioning that the red emission intensity continues to increase with the increased Eu3+ doping concentration, and the fluorescence lifetimes remain unchanged. These extraordinary phenomena mainly stem from the special concentration quenching mechanism in such two-phase mixing material, namely, the increased lattice interface barriers from Eu six-coordinated units and Eu eight-coordinated units can effectively block the non-radiation by enlarging the average distance between luminescent centers. The improved fluorescence thermal stability and suppressed non-radiative transition rate in NIMO:40%Eu3+ sample are further proving regulatory role of lattice interface barriers. In addition, a warm white light-emitting diode (LED) is successfully fabricated, exhibiting Commission Internationale de l'Eclairage (CIE) coordinates of (0.343, 0.335), a color rendering index (CRI) of 92.1, and a correlated color temperature (CCT) of 5013 K, showing significant application prospects for high-quality lighting devices.

Regulatory mechanisms and therapeutic implications of insulin-like growth factor 2 mRNA-binding proteins, the emerging crucial m6A regulators of tumors.

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) serve essential biological functions as post-transcriptional performers, participating in the acquisition or maintenance of tumor hallmarks due to their distinct protein structures. Emerging evidence indicates that IGF2BPs belong to the class III type of RNA N6-methyladenosine (m6A) modification readers, controlling RNA stability, storage, localization, metabolism, and translation in multiple vital bioprocesses, particularly tumorigenesis and tumor progression. Here, we discuss the underlying regulatory mechanisms and pathological functions of IGF2BPs which act as m6A readers in the context of tumor pathogenesis and multidrug resistance. Furthermore, we highlight the potential of IGF2BPs as drug targets in clinical tumor treatment. Hence, precise and novel tumor therapeutic approaches could be uncovered by targeting epigenetic heterogeneity.

Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways.

OBJECTIVE: Human oral squamous cell carcinoma (OSCC) is a major cause of mortality and morbidity worldwide. There is an urgent need to identify bioactive molecules and potential target genes that could inhibit carcinogenesis for OSCC therapy. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring flavonoid, has been previously shown to have anti-proliferative activities in OSCC; however, its molecular mechanism is unknown. METHODS: Colony formation, cell viability, Boyden chamber, wound healing, and tumor xenograft assays were used to detect the impact of fisetin on OSCC cells in vitro and in vivo. Western blot analysis was used to examine the corresponding protein expression. RESULTS: Fisetin treatment significantly inhibited proliferation and promoted apoptosis by repressing PAK4 expression. Moreover, fisetin treatment attenuated cell migration by blocking PAK4 signaling pathways. In addition, the tumor xenograft showed anti-tumor growth effects of fisetin exposure in vivo. CONCLUSION: Fisetin may represent a potential therapeutic strategy for human OSCC by targeting PAK4 signaling pathways.

MAGE-A11 Expression Predicts Patient Prognosis in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer worldwide. Growing evidence showed that Melanoma-associated antigen-A11 (MAGE-A11) was abnormally expressed in various malignancies, but MAGE-A11 expression and its biological roles in HNSCC had not been reported in detail. The aim of the study was to investigate the association between MAGE-A11 signatures and clinicopathological features of HNSCC patients and uncover its potential mechanisms in HNSCC patients. METHODS: In the present study, we analyzed the expression of MAGE-A11 gene and evaluated the impact of MAGE-A11 genes expression on clinical outcome from the Cancer Genome Atlas (TCGA) database. MAGE-A11 expression was assessed in a well-characterized series of HNSCC (N = 75) with long-term follow-up and 10 cases of adjacent non-cancerous tissues, which were diagnosed between 2013 and 2014, by using immunohistochemistry. The correlation between MAGE-A11 expression and clinicopathological factors was analyzed. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of MAGE-A11 expression among HNSCC patients. RESULTS: The results showed that MAGE-A11 mRNA expression was increased in HNSCC tissues compared to "normal" tissues (P < 10-12). MAGE-A11 protein expression was not correlated with lymph node status, relapse, age, gender, histological grade, differentiation, clinical stage, tumor size, radiotherapy or chemotherapy. The patients with high MAGE-A11 expression had lower 5-year overall survival (OS) rates than those with low MAGE-A11 expression as determined using the Kaplan-Meier method. The univariate and multivariate analyses confirmed that elevated MAGE-A11 was an independent prognostic factor for the OS of HNSCC patients. CONCLUSION: These findings indicate that MAGE-A11 may be a valuable diagnostic or prognostic marker as well as a potential molecular therapy target for HNSCC patients.