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Background: Cancer-associated fibroblasts (CAFs) are key components of the pancreatic adenocarcinoma (PAAD) tumor microenvironment (TME), where they promote tumor progression and metastasis through immunosuppressive functions. Although significant progress has been made in understanding the crosstalk between cancer cells and CAFs, many underlying mechanisms remain unclear. Recent studies have highlighted the importance of calcium signaling in enhancing interactions between tumor cells and the surrounding stroma, with the S100 family of proteins serving as important regulators. While the roles of some S100 proteins have been extensively studied, others, such as S100A13, remain less well understood. Methods: Bioinformatic analysis was employed to predict the pathogenic potential of CAFs and S100A13. Stable S100A13 knockdown CAFs were generated using a short hairpin RNA system. Cellular viability and apoptosis rates were evaluated through CCK-8 and flow cytometry tests, respectively. Additionally, the wound healing and migration assays were conducted to assess the invasive and metastatic capabilities. Transcriptome analysis was conducted to identify differential gene expression and associated signaling pathways in PAAD cells derived from an indirect culture system. Furthermore, the protumoral role of S100A13 in PAAD was further verified using both 3D bioprinting and cell line-based xenograft tumor models. Results: In this study, we identified a strong association between S100A13, a calcium-binding protein, and CAFs in PAAD. Gene expression analysis revealed that S100A13 was highly expressed in CAFs and correlated with poor prognosis. Knockdown of S100A13 in CAFs reduced the metastatic potential of PAAD cells. In addition, S100A13 depletion impaired cell motility and calcium signaling pathways within the TME. Furthermore, silencing S100A13 in CAFs markedly slowed PAAD progression in both tumor spheroids and Balb/c nude mice. Conclusions: Together, our findings underscore the critical role of CAFs-derived S100A13 in PAAD progression and suggest that targeting S100A13 may offer a promising therapeutic strategy for PAAD. [ABSTRACT FROM AUTHOR]

Marked by iron buildup and lipid peroxidation, ferroptosis is a relatively new regulatory cell death (RCD) pathway. Many diseases like cancer, myocardial ischemia-reperfusion injury (MIRI), neurological disorders and acute renal failure (AKI) are corelated with ferroptosis. The main molecular processes of ferroptosis discovered yet will be presented here, along with the approaches in which it interacts with tumour-associated signaling pathways and its uses in systemic therapy, radiation therapy, and immunotherapy managing tumors. [ABSTRACT FROM AUTHOR]

Background: Uterine Corpus Endometrial Carcinoma (UCEC) is a prevalent gynecologic malignancy with complex molecular underpinnings. This study identifies key woundhealing genes involved in UCEC and elucidates their roles through a comprehensive analysis. Methods: In silico and in vitro experiments. Results: Seventy wound healing-associated genes were extracted from the Gene Ontology (GO) database, and a protein-protein interaction (PPI) network was constructed using the STRING database. CytoHubba analysis in Cytoscape identified six pivotal hub genes: CD44, FGF2, FGF10, KDM6A, FN1, and MMP2. These genes exhibited significantly lower expression in UCEC cell lines compared to normal controls, as confirmed by RT-qPCR. Receiver Operating Characteristic (ROC) analysis demonstrated their potential as diagnostic biomarkers, with Area Under the Curve (AUC) values ranging from 0.94 to 1.00. Validation using TCGA datasets revealed consistent downregulation of these genes in UCEC samples, corroborated by immunohistochemical staining. Promoter methylation analysis showed significantly higher methylation levels in UCEC, correlating with decreased mRNA expression and poor survival outcomes. Genetic alteration analysis indicated frequent mutations in FN1 and KDM6A, although these did not significantly affect survival. Functional analysis using the CancerSEA database highlighted the involvement of these genes in critical cancer-related processes, including angiogenesis, apoptosis, and metastasis. Immune correlation studies revealed significant associations with immune inhibitor genes and distinct expression patterns across immune subtypes. Overexpression studies in UCEC cell lines demonstrated that CD44 and MMP2 reduce proliferative ability while enhancing migration and wound healing. Conclusion: Collectively, these findings underscore the crucial roles of CD44, FGF2, FGF10, KDM6A, FN1, and MMP2 in UCEC pathogenesis, highlighting their potential as biomarkers and therapeutic targets in this malignancy. [ABSTRACT FROM AUTHOR]

Structural maintenance of chromosome-1A (SMC1A) is overexpressed in various malignancies including triple-negative breast cancer (TNBC). As a core component of the cohesin complex, SMC1A was initially recognized for its involvement in chromosomal cohesion and DNA-repair pathways. However, recent studies have unveiled its pivotal role in epithelial–mesenchymal transition (EMT), metastasis, and chemo- and radio-resistance in cancer cells. In hepatocellular carcinoma, aberrant phosphorylation of SMC1A has been associated with enhanced cell proliferation and migration. Despite these insights, the precise role of SMC1A phosphorylation in breast cancer remains largely unexplored. This study represents the first investigation to test the phosphorylation status and subcellular localization of SMC1A (p-SMC1A) in breast cancer and normal breast tissues. Immunohistochemical (IHC) staining was conducted using previously validated phospho-SMC1A antibodies on a histological section and tissue microarray (TMA) comprising samples from primary, invasive, and metastatic breast cancer and normal breast tissues. Our results revealed that p-SMC1A staining intensity was lower in normal breast tissues compared to invasive or metastatic breast cancer tissues (p < 0.001). Approximately 40% of breast cancer tissue exhibited cytoplasmic/membranous localization of p-SMC1A, whereas nuclear expression was observed in normal breast tissues. Moreover, elevated phosphorylation levels were significantly associated with higher tumor grade and metastasis. [ABSTRACT FROM AUTHOR]

As research progresses, our understanding of the tumor microenvironment (TME) has undergone profound changes. The TME evolves with the developmental stages of cancer and the implementation of therapeutic interventions, transitioning from an immune-promoting to an immunosuppressive microenvironment. Consequently, we focus intently on the significant role of the TME in tumor proliferation, metastasis, and the development of drug resistance. AXL is highly associated with tumor progression; however, previous studies on AXL have been limited to its impact on the biological behavior of cancer cells. An increasing body of research now demonstrates that AXL can influence the function and differentiation of immune cells, mediating immune suppression and thereby fostering tumor growth. A comprehensive analysis to identify and overcome the causes of immunosuppressive microenvironments represents a novel approach to conquering cancer. In this review, we focus on elucidating the role of AXL within the immunosuppressive microenvironments, discussing and analyzing the effects of AXL on tumor cells, T cells, macrophages, natural killer (NK) cells, fibroblasts, and other immune-stromal cells. We aim to clarify the contributions of AXL to the progression and drug resistance of cancer from its functional role in the immune microenvironment. [ABSTRACT FROM AUTHOR]

Bcl-2, a key regulator of cellular apoptosis, is typically linked to adverse prognosis in solid tumors due to its inhibition of apoptotic cell death and promotion of cellular proliferation, leading to tumor progression. However, studies on Bcl-2 in breast cancer have shown inconsistent results, with some indicating favorable outcomes. This study aims to determine the subtype-specific role of Bcl-2 in breast cancer. Female breast cancer patients who completed primary treatment at Wonju Severance Hospital, Korea, from 2004 to 2018 were included. Clinicopathological characteristics, including Bcl-2 expression, were collected, and patients were classified based on Bcl-2 expression in more than or less than 10% of tumor cells. Kaplan–Meier curves compared recurrence-free interval (RFI) and overall survival (OS). The final cohort of 617 patients, with a mean age of 54.79 ± 11.2 years, showed no overall survival difference by Bcl-2 status (p = 0.616). In HER2-overexpressed patients, high Bcl-2 expression was linked to poor prognosis (p = 0.0021). This trend appeared in ER-positive (p = 0.297) and ER-negative (p = 0.029) subgroups. Conversely, in HER2-negative patients, Bcl-2 overexpression indicated better survival (p = 0.009), consistent in ER-positive (p = 0.259) and ER-negative (p = 0.010) subgroups. Bcl-2's impact on survival varies with HER2 status, showing poor prognosis in HER2-overexpressed and better prognosis in HER2-negative patients. [ABSTRACT FROM AUTHOR]

Enriched iron metabolic features such as high transferrin receptor (TfR) expression and high iron content are commonly observed in aggressive gliomas and can be associated with poor clinical responses. However, the underlying question of how iron contributes to tumor aggression remains elusive. Gliomas harboring isocitrate dehydrogenase (IDH) mutations account for a high percentage (>70 %) of recurrent tumors and cells with an acquired IDH mutation have been reported to have increased motility and invasion. This study aims to investigate how an acquired IDH mutation modulates iron metabolism and the implication(s) of iron on tumor cell growth. IDH mutant cells (U87R132H) grow significantly faster which is accompanied with increased TfR expression and iron uptake in vitro compared to wild-type U87 cells. This phenotype is retained in vivo. Biomechanically, U87R132H cells are significantly less stiff and supplementation with ferrous ammonium sulfate (Fe2+) augments membrane fluidity to drive U87R132H cells into a super motile state. These findings provide insight into how an acquired IDH mutation may be able to modulate iron metabolism, allowing iron to serve as a biomechanical driver of tumor progression. [Display omitted] • Isocitrate dehydrogenase (IDH)-mutant glioma preferentially accumulate iron. • IDH-mutant glioma exhibit iron-dependent growth. • Iron modulates IDH-mutant glioma membrane fluidity to promote tumor cell motility. [ABSTRACT FROM AUTHOR]

Purpose: Histone deacetylase 6 (HDAC6) plays a critical role in tumorigenesis and tumor progression, contributing to proliferation, chemoresistance, and cell motility by regulating microtubule architecture. Despite its upregulation in melanoma tissues and cell lines, the specific biological roles of HDAC6 in melanoma are not well understood. This study aims to explore the functional effects and underlying mechanisms of WT161, a selective HDAC6 inhibitor, in melanoma cell lines. Methods: Cell proliferation was assessed using both 2D and 3D cell culture systems, including MTT assays, spheroid growth analyses, and colony formation assays. The interaction between WT161 and the chemotherapeutic agents temozolomide (TMZ) or dacarbazine (DTIC) was evaluated using the Chou-Talalay method. Apoptotic cell death was analyzed through flow cytometry, while migration, adhesion, and invasion assays were conducted to evaluate the motility capacities of melanoma cells. Western blot assays quantified α-tubulin acetylation (Lys40), PARP cleavage, and protein levels of β-catenin and E-cadherin. Results: WT161 significantly reduced cell growth in both 2D and 3D cultures, decreased clonogenic capacity, and showed synergistic interactions with TMZ and DTIC. The inhibitor also induced apoptotic cell death and enhanced TMZ-induced apoptosis. Additionally, WT161 reduced cell migration and invasion while increasing cell adhesion. These effects were linked to changes in β-catenin and E-cadherin levels, depending on the specific cell type evaluated. Conclusion: Our study underscores the pivotal role of HDAC6 in melanoma progression, establishing it as a promising therapeutic target. We provide the first comprehensive evidence of WT161’s anti-melanoma effects, setting the stage for further research into HDAC6 inhibitors as a potential strategy for melanoma treatment. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a potential unfavorable prognostic factor in neuroendocrine tumors (NETs); conversely, statins proved to have antiproliferative effects in NET cell lines and could be a helpful therapeutic strategy for these patients. The main objective of this observational cohort retrospective study is to explore the associations between dyslipidemia and NET progression and evaluate the potential influence of statins in this context. 393 patients with histologically confirmed gastroenteropancreatic or bronchopulmonary NETs from six Italian centres didicated to NET diagnosis and therapy were included. The cohort included 123 patients with dyslipidemia, 81 of which were taking statins. Clinicopathological data, including patient demographics, tumor characteristics, and treatment details as well as the prevalence, timing of dyslipidemia and hypolipemic therapy were collected. The main outcome measure used is progression‐free survival (PFS). Among the 393 patients, 123 (31.3%) had dyslipidemia. Statins were used by 81 (65.8%) dyslipidemic patients, mostly atorvastatin. Median PFS was 87 months overall, 124 months in non‐dyslipidemic patients, and 72 months in dyslipidemic patients (p = .268). Dyslipidemic patients on statins had a significantly better median PFS (108 months) than those not on statins (26 months; p = .024). Recurrence‐free survival (RFS) was also evaluated, but no significant differences were found. In conclusion, while PFS was lower in dyslipidemic patients compared to non‐dyslipidemic patients, the difference was not statistically significant. Statin therapy was associated with improved PFS among dyslipidemic patients, suggesting a potential antiproliferative effect of statins in NETs. These findings warrant further investigation to substantiate the role of statins in the management of NETs. [ABSTRACT FROM AUTHOR]

Glioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression. This led to the hypothesis that GPx4 expression negatively influences GBM cell growth. This study utilizes a doxycycline inducible GPx4 overexpression model to test this hypothesis. Consistently, the overexpression of GPx4 significantly impairs cell growth and colony formation while also causing an accumulation of cells in G1/G0 phase of the cell cycle. From a biophysical perspective, GPx4 overexpressing cells have significantly greater surface area, increased Young's modulus, and experience anomalous sub-diffusion as opposed to normal diffusion associated with Brownian motion. Moreover, analysis of patient derived GBM cells reveal that cell growth rates, plating efficiency, and Young's modulus are all inversely proportional to GPx4 expression. Therefore, GPx4 appears to be a biophysical regulator of GBM cell growth that warrants further mechanistic investigation in its role in GBM progression. [ABSTRACT FROM AUTHOR]

Objective: Hepatocellular carcinoma (HCC) represents a severe and aggressive malignancy with a poor prognosis, characterized by high incidences of illness and death, making it a critical issue for global health. Tyrosyl-tRNA synthetase 1 (YARS1) is known to be upregulated across various cancers and is considerably linked to tumorigenesis. However, the detailed functions and molecular mechanisms of YARS1 in HCC remain unclear. This research explores the expression of YARS1 in HCC and its role in promoting tumor progression through the yes-associated protein 1 (YAP1) pathway. Material and Methods: The potential role and diagnostic significance of YARS1 and YAP1 in HCC were analyzed using relevant datasets. Subsequently, we constructed HCC cell lines with stable knockdown or overexpression of YARS1. In vitro , we used Cell Counting Kit-8 and colony formation assays to examine cell proliferation, terminal deoxynucleotidyl transferase dUTP nick end labeling assays to detect apoptosis, and Transwell migration and invasion assays to assess cell metastasis. Western blotting was employed to analyze the molecular mechanisms. Finally, we developed a lung metastasis model for HCC to assess the impact of YARS1 and YAP1 on tumor spread in a living organism, as well as their interrelationship. Results: The findings revealed a notable increase in YARS1 expression in HCC tumors, associated with a worse prognosis. In vitro , YARS1 overexpression significantly increased HCC cell proliferation and metastasis when reducing apoptosis (P < 0.001). In addition, YARS1 overexpression accelerated HCC growth in vivo. Further experiments demonstrated that silencing YAP1 effectively reversed the effects of YARS1 on HCC cell invasion (P < 0.01), apoptosis inhibition (P < 0.01), and metastasis (P < 0.001). Conclusion: In summary, this research reveals that YARS1 enhances the malignant progression of HCC through the activation of the YAP1 signaling pathway. Elevated levels of YARS1 in HCC are strongly linked to poor prognosis, indicating that YARS1 might serve as a new therapeutic target for HCC. Future studies should investigate additional mechanisms of YARS1 in HCC and create targeted therapies to improve outcomes for HCC patients. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (LncRNAs) are crucial regulators of gene expression and cellular processes, with significant implications for cancer research. This review focuses on the role of LncRNA CARMN (Cardiac Arrest and Regulated Myocyte Nuclear Protein) in various cancers. CARMN, originally identified for its function in cardiac tissues, has shown dysregulated expression in several tumor types, including cervical, breast, colorectal, and esophageal cancers. Its altered expression often correlates with tumor progression, metastasis, and patient prognosis, suggesting its potential as both a biomarker and therapeutic target. In cervical cancer, CARMN's role as a tumor suppressor is highlighted by its ability to inhibit cell proliferation, migration, and invasion through interaction with the miR-92a-3p/BTG2 axis and modulation of the Wnt/β-catenin signaling pathway. In breast cancer, CARMN acts as an enhancer RNA, affecting epithelial-mesenchymal transition and metastasis by regulating MMP2 via DHX9. The downregulation of CARMN in triple-negative breast cancer is associated with enhanced sensitivity to chemotherapy. In colorectal cancer, CARMN's expression is regulated by m6A methylation and mutant p53, influencing tumor growth through miR-5683 and FGF2. Lastly, in esophageal cancer, genetic variations in CARMN affect cancer susceptibility, with certain SNPs and haplotypes associated with either increased or decreased risk. Additionally, the relationship between CARMN and immune cell dynamics highlights its potential role in cancer immune surveillance and therapy. Finally, we found that CARMN may regulate immune cell exhaustion in the tumor microenvironment by influencing the recruitment and activation of NK cells and T cells, as well as modulating macrophage polarization. This review emphasizes the diverse roles of CARMN across different cancers and its potential as a diagnostic and therapeutic tool. Future research should address the mechanistic details of CARMN's involvement in cancer, validate its clinical utility, and explore its therapeutic potential in combination with existing treatments. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most significant oncological threats to human health globally. Patients often exhibit a high propensity for tumor recurrence and metastasis post-surgery, resulting in suboptimal prognoses. One of the underlying reasons for the metastatic potential of CRC is the sustained abnormal state of the tumor immune microenvironment, particularly characterized by the atypical death of critical immune cells. In recent years, a novel concept of cell death known as PANoptosis has emerged. This form of cell death is regulated by the PANoptosome complex and encompasses key features of apoptosis, pyroptosis, and necroptosis, yet cannot be entirely substituted by any of these processes alone. Due to its widespread occurrence and complex mechanisms, PANoptosis has been increasingly reported in various malignancies, enhancing our understanding of its pathological mechanisms, particularly in the context of CRC. However, the characteristics of immune cell PANoptosis within the CRC immune microenvironment have not been thoroughly elucidated. In this review, we focus on the impact of CRC progression on various immune cell types and summarize the distinctive features of immune cell PANoptosis. Furthermore, we highlight the future research trends and challenges associated with the mechanisms of immune cell PANoptosis in CRC. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has emerged as a novel clinical therapeutic option for a variety of solid tumors over the past decades. The application of immunotherapy in primary and metastatic brain tumors continues to grow despite limitations due to the physiological characteristics of the immune system within the central nervous system (CNS) and distinct pathological barriers of malignant brain tumors. The post-immunotherapy treatment imaging is more complex. In this review, we summarize the clinical application of immunotherapies in solid tumors beyond the CNS. We provide an overview of current immunotherapies used in brain tumors, including immune checkpoint inhibitors (ICIs), oncolytic viruses, vaccines, and CAR T-cell therapies. We focus on the imaging criteria for the assessment of treatment response to immunotherapy, and post-immunotherapy treatment imaging patterns. We discuss advanced imaging techniques in the evaluation of treatment response to immunotherapy in brain tumors. The imaging characteristics of immunotherapy treatment-related complications in CNS are described. Lastly, future imaging challenges in this field are explored. [ABSTRACT FROM AUTHOR]

Background: Sentrin/SUMO-specific protease 3 (SENP3) is essential to regulate protein stability and function in normal and cancer cells. Nevertheless, its role and action mechanisms in prostate cancer (PCa) remain elusive. Thus, clarification of SENP3's involvement and the SUMOylation process in PCa is pivotal for discovering potential targets and understanding SUMOylation dynamics. Methods: Cell viability, EdU staining, live cell imaging, and cell cycle assays were used to determine proliferation of PCa cells. Transwell and wound-healing assays were used to detect migration of PCa cells. The interaction between SENP3 and SIX1 was determined by co-immunoprecipitation, western blotting, and immunofluorescence assays. Xenograft models established on NOD-SCID mice were used to evaluate in vivo effects post SENP3 knockdown. Immunohistochemistry was performed to investigate the expression of SENP3 in PCa tissues. Results: This study found that SENP3 is highly expressed in PCa cell lines and tissues from PCa patients. Overexpressed SENP3 is associated with metastatic malignancy in PCa. Various in vivo and in vitro experiments confirmed that SENP3 promotes the proliferation and migration of PCa. In addition, SENP3 interacts with the SD domain of SIX1 and mediates its deSUMOylation and protein stability. Lys154 (K154) is required for the SUMOylation of SIX1. More importantly, SENP3 promotes the malignancy of PCa through the regulation of SIX1. Conclusions: We unravel the significant role of SENP3 in regulating protein stability of SIX1 and progression of PCa, which may deepen our understanding of the SUMOylation modification and provide a promising target for management of metastatic PCa. [ABSTRACT FROM AUTHOR]

Objectives: B7 homolog 3 protein (B7-H3, also known as CD276) is a member of the B7 family that has been found to be associated with the growth and progression of a variety of tumors, but no pan-cancer evaluations of CD276 have been performed so far. In this study, we aimed to perform a pan-cancer analysis of the oncogenic role of CD276 in human tumors; Methods: We used a series of databases to perform a pan-cancer analysis of CD276, including the expression level of CD276 in pan-cancer and its relationship to tumor progression, patient survival duration, the immune cell infiltration within the tumor, and the potential signaling pathways and molecular mechanisms associated with CD276; Results: We found that CD276 was a potential biomarker for the prognosis of most cancers. The high expression of CD276 was associated with tumor progression, leading to poor survival. Notably, the up-regulation of CD276 expression in tumors increased the tumor infiltration of cancer-associated fibroblasts (CAFs) and myeloid-derived suppressor cells (MDSCs) and decreased the CD8+ T cells; Conclusions: Our study demonstrates that CD276 might promote tumor progression via the promotion of an immunosuppressive microenvironment. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) has significantly extended the lifespan of people living with Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS), thereby transforming the disease into a manageable chronic condition. However, this increased longevity has led to a higher incidence of non-AIDS-defining cancers (NADCs) among this population. In this holistic review, we explore the complex interactions between HIV, ART, and cancer development, focusing on how ART influences tumor initiation and progression in people living with HIV/AIDS (PLWHA). Our findings from this reveal several critical aspects of cancer risk in PLWHA. Firstly, while ART restores immune function, it does not fully normalize it. Chronic immune activation and persistent inflammation continue to be prevalent, creating a conducive environment for oncogenesis. Additionally, PLWHA are more susceptible to persistent infections with oncogenic viruses such as human papillomavirus (HPV) and Epstein–Barr virus (EBV), further increasing cancer risk. Some ART drugs have been implicated in genotoxicity and mitochondrial dysfunction, potentially promoting tumorigenesis. ART-induced metabolic changes, including insulin resistance and dyslipidemia, are also associated with heightened cancer risk. Common NADCs in PLWHA include lung cancer, liver cancer, anal cancer, and Hodgkin lymphoma, each with distinct etiologies linked to both HIV-related and ART-related factors. The interplay between HIV infection, chronic inflammation, immune restoration via ART, and the direct effects of ART drugs creates a unique cancer risk profile in PLWHA. Although ART reduces the incidence of AIDS-defining cancers, it does not confer the same protective effect against NADCs. Persistent HIV-related inflammation and immune activation, despite viral suppression, are key factors in cancer development. Additionally, long-term exposure to ART may introduce new oncogenic risks. These insights highlight the need for integrated cancer screening and prevention strategies tailored to PLWHA. Future research is needed to focus on identifying biomarkers for early cancer detection and developing ART regimens with lower oncogenic potential. Healthcare providers should be vigilant in monitoring PLWHA for cancer and adopt comprehensive screening protocols to mitigate the increased cancer risk associated with ART. [ABSTRACT FROM AUTHOR]

Background. Clinical diagnosis of papillary thyroid cancer usually occurs at the stage of tumor progression accompanied by intensive processes of growth, invasion, formation of blood vessels to provide blood supply to the tumor, the structure and quantitative changes of which can be more informatively accurately assessed by polarization biomedical optics. The purpose of the study was to substantiate the possibility of using polarization biomedical optics methods in the diagnosis of papillary thyroid cancer based on the principles of comprehensiveness and integrated pathophysiology. Materials and methods. Two groups of patients were studied: the control group — healthy donors (n = 51), the experimental group — patients with papillary thyroid cancer (n = 51) who underwent a puncture biopsy of the thyroid gland for diagnostic purposes using the fundamental idea of polarization biomedical optics with two analytical approaches — statistical and topographic (multifractal). Instrumental laser methods were used: polarization, interference, digital holographic. The statistical parameters of polarization azimuth maps, polarization azimuth of phase and multifractal spectra of digital microscopic images of native histological sections of thyroid biopsy from patients with papillary cancer were quantitatively evaluated with the determination of average, dispersion, asymmetry and excess. The significance of differences compared to the control, taken as 100 % was assessed using the Student’s parametric test (p < 0.05). Results. A significant increase in the asymmetry and excess of the polarization azimuth, a significant inhibition of the average polarization azimuth of phase digital microscopic images of native histological sections of thyroid biopsy from patients with papillary cancer, a significant increase in the asymmetry and excess of phase digital microscopic images of native histological sections of thyroid biopsy from patients with papillary cancer were revealed. A significant increase in dispersion and a probable decrease in the asymmetry and excess of multifractal spectra of polarization azimuth maps of digital microscopic images of native histological sections of thyroid biopsy in patients with papillary cancer were shown. Conclusions. A significant increase in the biophysical optical parameters of digital microscopic images of native histological sections of thyroid biopsy of patients with papillary cancer was found due to increased growth of connective tissue around transformed T thyrocytes and blood vessels to provide their nutrition. A probable inhibition of the average azimuth of polarization of phase digital microscopic images of native histological sections of thyroid biopsy of patients with papillary cancer and a probable decrease in the asymmetry and excess of multifractal spectra of polarization azimuth maps of digital microscopic images of native histological sections of thyroid biopsy of patients with papillary cancer are caused by papillary proliferation of transformed T thyrocytes as an amorphous component in patients with papillary cancer as a result of activation of tumor progression with intensive processes of growth, invasion, and formation of blood vessels to provide blood supply to the tumor. [ABSTRACT FROM AUTHOR]

Introduction: Preclinical evidence suggests that host obesity is associated with tumor progression due to immuno-metabolic dysfunction, but the impact of obesity on immunity and clinical outcomes in patients is poorly understood, with some studies suggesting an obesity paradox. We recently reported that high-adiposity and low-muscle body composition phenotypes are associated with striking increases in epithelial ovarian cancer (EOC) mortality and we observed no evidence of an obesity paradox. However, whether at-risk versus optimal body composition phenotypes are associated with distinct immuno-metabolic milieus remains a fundamental gap in knowledge. Herein, we defined differentially abundant circulating immuno-metabolic biomarkers according to body composition phenotypes in EOC. Methods: Muscle and adiposity cross-sectional area (cm2) was assessed using CT images from 200 EOC patients in The Body Composition and Epithelial Ovarian Cancer Survival Study at Roswell Park. Adiposity was dichotomized as low versus high; patients with skeletal muscle index (SMI) <38.5 (muscle cm2/height m2) were classified as low SMI (sarcopenia). Joint-exposure phenotypes were categorized as: Fit (normal SMI/low-adiposity), Overweight/Obese (normal SMI/high-adiposity), Sarcopenia/Obese (low SMI/high adiposity), and Sarcopenia/Cachexia (low SMI/low-adiposity). Treatment-naïve serum samples were assessed using Biocrates MxP Quant 500 for targeted metabolomics and commercially available Luminex kits for adipokines and Th1/Th2 cytokines. Limma moderated T-tests were used to identify differentially abundant metabolites and cytokines according to body composition phenotypes. Results: Patients with 'risk' phenotypes had significantly increased abundance of metabolites and cytokines that were unique according to body composition phenotype. Specifically, the metabolites and cytokines in increased abundance in the at-risk phenotypes are implicated in immune suppression and tumor progression. Conversely, increased abundance of lauric acid, IL-1β, and IL-2 in the Fit phenotype was observed, which have been previously implicated in tumor suppression and anti-tumor immunity. Conclusion: In this pilot study, we identified several significantly differentially abundant metabolites according to body composition phenotypes, confirming that clinically significant joint-exposure body composition phenotypes are also biologically distinct. Although we observed evidence that at-risk phenotypes were associated with increased abundance of immuno-metabolic biomarkers indicated in immune suppression, additional confirmatory studies focused on defining the link between body composition and immune cell composition and spatial relationships in the EOC tumor microenvironment are warranted. [ABSTRACT FROM AUTHOR]

Candida albicans is an "opportunistic fungal agent" in cancer patients that can become colonized in both mucosal and deep tissues and cause severe infections. Most evidence has shown that C. albicans can enhance the progress of different cancers by several mechanisms such as generating virulence factors, participation in endogenous production of pro-inflammatory mediators, and stimulating a wide range of immune cells in the host. The main idea of this review is to describe a range of Candida-used mechanisms that are important in candidiasis-associated malignant processes and cancer development, particularly breast cancer. This review intends to provide a detailed discussion on different regulatory mechanisms of C. albicans that undoubtedly help to open new therapeutic horizons of cancer therapy in patients with fungal infection. The current therapeutic approach is not fully effective in immunocompromised and cancer patients, and further studies are required to find new products with effective antifungal properties and minimal side effects to increase the susceptibility of opportunistic fungal infections to conventional antifungal agents. So, in this situation, a special therapy should be considered to control the infection and simultaneously have the most therapeutic index on tumor patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • RNA binding proteins (RBPs) impact tumor development and play a role in sorting noncoding RNAs (ncRNAs) into exosomes. • The RBP-ncRNA-exosome mechanism is crucial in tumor regulation and provides insights for innovative treatment strategies. • This mechanism influences tumor metastasis, multidrug resistance, angiogenesis, the immunosuppressive microenvironment, and tumor progression. • Potential therapeutic strategies include targeted drug discovery and genetic engineering of therapeutic exosomes. RNA binding proteins (RBPs) play a role in sorting non-coding RNAs (ncRNAs) into exosomes. These ncRNAs, carried by exosomes, are involved in regulating various aspects of tumor progression, including metastasis, angiogenesis, control of the tumor microenvironment, and drug resistance. Recent studies have emphasized the importance of the RBP-ncRNA-exosome mechanism in tumor regulation. This comprehensive review aims to explore the RBP-ncRNA-exosome mechanism and its influence on tumor development. By understanding this intricate mechanism provides novel insights into tumor regulation and may lead to innovative treatment strategies in the future. The review discusses the formation of exosomes and the complex relationships among RBPs, ncRNAs, and exosomes. The RBP-ncRNA-exosome mechanism is shown to affect various aspects of tumor biology, including metastasis, multidrug resistance, angiogenesis, the immunosuppressive microenvironment, and tumor progression. Tumor development relies on the transmission of information between cells, with RBPs selectively mediating sorting of ncRNAs into exosomes through various mechanisms, which in turn carry ncRNAs to regulate RBPs. The review also provides an overview of potential therapeutic strategies, such as targeted drug discovery and genetic engineering for modifying therapeutic exosomes, which hold great promise for improving cancer treatment. [ABSTRACT FROM AUTHOR]

Objective To explore the specific role and molecular mechanism of octamer-binding transcription factor 4 (Oct4) in promoting the progression of esophageal squamous cell carcinoma and radioresistance. Methods The Gene Expression Profile Data Dynamic Analysis (GEPIA) database was used to analyze the expression differences of the Oct4 gene in different types of tumor tissues and their corresponding adjacent normal tissues. The clinical data and surgical resection tissue specimens of 196 patients with esophageal squamous cell carcinoma who received surgery combined with radiotherapy at Henan Provincial Chest Hospital from January 2013 to May 2022 were collected. Immunohistochemistry was used to detect the expression of Oct4 protein in the tumor and adjacent tissues. The lentiviral packaging system was used to construct esophageal squamous cell carcinoma cell lines that up-regulated or down-regulated Oct4. The cell counting kit 8 (CCK-8) was used to detect the cell proliferation ability, the scratch test was used to detect the cell migration ability, and the clone formation test was used to detect the cell radiosensitivity. Immunofluorescence experiment was used to detect DNA damage level, and Western blot was used to detect the expressions of Oct4, human phosphorylated histone (γ-H2AX), E-cadherin, N-cadherin, vimentin, and zinc finger E box binding homology box 1 (ZEB1). Results The analysis of GEPIA database showed that the expression level of Oct4 mRNA in esophageal carcinoma was higher than that in paracancerous tissues. The expression level of Oct4 protein in tumor tissues was 78.35±1.42, which was higher than that in adjacent tissues (16.27±0.49). The survival time of patients with a high expression of Oct4 was significantly shorter than that of patients with a low expression of Oct4 (25.40 and 47.00 months). Compared with the control group, the proliferation ability of KYSE510 cells in the Oct4 up-regulated group was enhanced after 72-h culture, and the cell migration ability of these cells was also enhanced, with the migration rate being (41.67±1.20)% vs (23.67±1.86)% after 24-h culture. The radiosensitivity of cells in this group decreased, with the radiosensitivity enhancement ratio being 0.69±0.06 vs 1.00±0.02. After radiotherapy, the expressions of γ-H2AX and E-cadherin decreased, while the expressions of ZEB1, vimentin and N-cadherin increased. Compared with the control group, the proliferation ability of KYSE150 cells in the Oct4 down-regulated groups 1 and 2 decreased (absorbance being 2.51±0.17, 2.38±0.16, and 3.33±0.07, respectively, P<0.01) after 72-h culture, and the migration ability also decreased, with the migration rate being (13.33± 0.88)%, (13.00±1.00)%, and (40.33±2.03)%, respectively (all P<0.001), after 24-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.34±0.11, 1.24± 0.07, and 1.00±0.02, respectively (all P<0.05). After radiotherapy, the expressions of γ -H2AX and E-cadherin increased, while the expressions of ZEB1, vimentin and N-cadherin decreased. Compared with the control group, the proliferation ability of KYSE510 cells in the ZEB1 down-regulated group decreased [absorbance being 1.33±0.15 vs 1.81±0.16 (P=0.002)] after 72-h culture. The radiosensitivity was enhanced, with the radiosensitivity enhancement ratio being 1.37±0.11 vs 1.00±0.01 (P=0.037), and after radiotherapy the expression of γ -H2AX increased. Conclusion Oct4 is involved in the regulation of epithelial-mesenchymal transformation of esophageal squamous cell carcinoma, which promotes the proliferation, migration, and radioresistance of esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits the growth of hepatocellular carcinoma (HCC) cells and enhances their sensitivity to ferroptosis induced by RAS-selective lethal 3 (RSL3), a compound known to cause ferroptosis. MDH2 knock-down enhances RSL3-induced intracellular reactive oxygen species, free iron ions and lipid per-oxides levels, leading to HCC ferroptotic cell death which is rescued by ferrostatin-1 and iron chelator deferiprone. Importantly, the inhibition of HCC cell growth caused by MDH2 deficiency is partially rescued by ferroptosis blockade. Mechanistically, MDH2 resists RSL3-induced ferroptosis sensitivity dependent on glutathione peroxidase 4 (GPX4), an enzyme responsible for scavenging lipid peroxides, which is stabilized by MDH2 in HCC. The protein expressions of MDH2 and GPX4 are positively correlated with each other in HCC cell lines. Furthermore, through our UALCAN website analysis, we found that MDH2 and GPX4 are highly expressed in HCC samples. These findings reveal a critical mechanism by which HCC evades ferroptosis via MDH2-mediated stabilization of GPX4 to promote tumor progression and underscore the potential of MDH2 inhibition in combi-nation with ferroptosis inducers for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Introduction: Multiple myeloma (MM) is an incurable hematological malignancy with high chromosome instability and heavy dependence on the immunosuppressive bone marrow microenvironment. P53 mutations are adverse prognostic factors in MM; however, clinically, some patients without P53 mutations also exhibit aggressive disease progression. DNp73, an inhibitor of TP53 tumor suppressor family members, drives drug resistance and cancer progression in several solid malignancies. Nevertheless, the biological functions of DNp73 and the molecular mechanisms in myelomagenesis remain unclear. Methods: The effects of DNp73 on proliferation and drug sensitivity were assessed using flow cytometry and xenograft models. To investigate the mechanisms of drug resistance, RNA-seq and ChIP-seq analyses were performed in MM cell lines, with validation by Western blot and RT-qPCR. Immunofluorescence and transwell assays were used to assess DNA damage and cell invasion in MM cells. Additionally, in vitro phagocytosis assays were conducted to confirm the role of DNp73 in immune evasion. Results: Our study found that activation of NF-kB-p65 in multiple myeloma cells with different p53 mutation statuses upregulates DNp73 expression at the transcriptional level. Forced expression of DNp73 promoted aggressive proliferation and multidrug resistance in MM cells. Bulk RNA-seq analysis was conducted to assess the levels of MYCN, MYC, and CDK7. A ChIP-qPCR assay was used to reveal that DNp73 acts as a transcription factor regulating MYCN gene expression. Bulk RNA-seq analysis demonstrated increased levels of MYCN, MYC, and CDK7 with forced DNp73 expression inMMcells. A ChIP-qPCR assay revealed that DNp73 upregulates MYCN gene expression as a transcription factor. Additionally, DNp73 promoted immune evasion of MM cells by upregulating MYC target genes CD47 and PD-L1. Blockade of the CD47/SIRPa and PD-1/PD-L1 signaling pathways by the SIRPa-Fc fusion protein IMM01 and monoclonal antibody atezolizumab significantly restored the anti-MM activity of macrophages and T cells in the microenvironment, respectively. Discussion: In summary, our study demonstrated for the first time that the p53 family member DNp73 remarkably induces proliferation, drug resistance, and immune escape of myeloma cells by directly targeting MYCN and regulating the MYC pathway. The oncogenic function of DNp73 is independent of p53 status in MMcells. These data contribute to a better understanding of the function of TP53 and its family members in tumorigenesis. Moreover, our study clarified that DNp73 overexpression not only promotes aggressive growth of tumor cells but, more importantly, promotes immune escape of MM cells through upregulation of immune checkpoints. DNp73 could serve as a biomarker for immunotherapy targeting PD-L1 and CD47 blockade in MM patients. [ABSTRACT FROM AUTHOR]

The gene inhibin subunit beta B (INHBB) encodes the inhibin βB subunit, which is involved in forming protein members of the transforming growth factor-β (TGF-β) superfamily. The TGF-β superfamily is extensively involved in cell proliferation, differentiation, adhesion, movement, metabolism, communication, and death. Activins and inhibins, which belong to the TGF-β superfamily, were first discovered in ovarian follicular fluid. They were initially described as regulators of pituitary follicle-stimulating hormone (FSH) secretion both in vivo and in vitro. Later studies found that INHBB is expressed not only in reproductive organs such as the ovary, uterus, and testis but also in numerous other organs, including the brain, spinal cord, liver, kidneys, and adrenal glands. This wide distribution implies its involvement in the normal physiological functions of various organs; however, the mechanisms underlying these functions have not yet been fully elucidated. Recent studies suggest that INHBB plays a significant, yet complex role in tumorigenesis. It appears to have dual effects, promoting tumor progression in some contexts while inhibiting it in others, although these roles are not yet fully understood. In this paper, we review the different expression patterns, functions, and mechanisms of INHBB in normal and tumor tissues to illustrate the research prospects of INHBB in tumor progression. Key points: • INHBB is a gene that encodes the inhibin βB subunit, which forms part of the TGF-β superfamily of proteins that regulate various cellular processes. • INHBB was initially discovered as a regulator of FSH secretion in reproductive organs, but it was later found to be expressed in many other organs and involved in their normal physiological functions. • INHBB has an emerging role in tumorigenesis, but the direction of this role is unclear and may vary depending on the tissue type and context. • This paper reviews the different expression patterns, functions, and mechanisms of INHBB in normal and tumor tissues, and suggests future research directions for INHBB in tumor progression. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the most common gynecological cancer in the developed world. However, the accuracy of current diagnostic methods is still unsatisfactory and time-consuming. Here, we presented an alternate approach to monitoring the progression of endometrial cancer via multiphoton microscopy imaging and analysis of collagen, which is often overlooked in current endometrial cancer diagnosis protocols but can offer a crucial signature in cancer biology. Multiphoton microscopy (MPM) based on the second-harmonic generation and two-photon excited fluorescence was introduced to visualize the microenvironment of endometrium in normal, hyperplasia without atypia, atypical hyperplasia, and endometrial cancer specimens. Furthermore, automatic image analysis based on the MPM image processing algorithm was used to quantify the differences in the collagen morphological features among them. MPM enables the visualization of the morphological details and alterations of the glands in the development process of endometrial cancer, including irregular changes in the structure of the gland, increased ratio of the gland to the interstitium, and atypical changes in the glandular epithelial cells. Moreover, the destructed basement membrane caused by gland proliferation and fusion is clearly shown in SHG images, which is a key feature for identifying endometrial cancer progression. Quantitative analysis reveals that the formation of endometrial cancer is accompanied by an increase in collagen fiber length and width, a progressive linearization and loosening of interstitial collagen, and a more random arrangement of interstitial collagen. Observation and quantitative analysis of interstitial collagen provide invaluable information in monitoring the progression of endometrial cancer. Label-free multiphoton imaging reported here has the potential to become an in situ histological tool for effective and accurate early diagnosis and detection of malignant lesions in endometrial cancer. [ABSTRACT FROM AUTHOR]

Anne Ließem, Uwe Leimer, Günter K Germann, Eva Köllensperger Clinic for Plastic, Aesthetic and Reconstructive Surgery, Spine, Orthopedic and Hand Surgery, Preventive Medicine – ETHIANUM, Heidelberg, 69115, GermanyCorrespondence: Eva Köllensperger, Clinic for Plastic, Aesthetic and Reconstructive Surgery, Spine, Orthopedic and Hand Surgery, Preventive Medicine – ETHIANUM, Heidelberg, 69115, Germany, Email Eva.Koellensperger@ethianum.deBackground: Adipokines, bioactive peptides secreted by adipose tissue, appear to contribute to breast cancer development and progression. While numerous studies suggest their role in promoting tumor growth, the exact mechanisms of their involvement are not yet completely understood.Methods: In this project, varying concentrations of recombinant human adipokines (Leptin, Lipocalin-2, PAI-1, and Resistin) were used to study their effects on four selected breast cancer cell lines (EVSA-T, MCF-7, MDA-MB-231, and SK-Br-3). Over a five-day proliferation phase, linear growth was assessed by calculating doubling times and malignancy-associated changes in gene and protein expression were identified using quantitative TaqMan real-time PCR and multiplex protein analysis. Migration and invasion behaviors were quantified using specialized Boyden chamber assays.Results: We found significant, adipokine-mediated genetic and proteomic alterations, with PCR showing an up to 6-fold increase of numerous malignancy-associated genes after adipokine-supplementation. Adipokines further altered protein secretion, such as raising the concentrations of different tumor-associated proteins up to 13-fold. Effects on proliferation varied, however, with most approaches showing significant enhancement in growth kinetics. A concentration-dependent increase in migration and invasion was generally observed, with no significant reductions in any approaches.Conclusion: We could show a robust promoting effect of several adipokines on different breast cancer cells in vitro. Understanding the interaction between adipose tissue and breast cancer cells opens potential avenues for innovative breast cancer prevention and therapy strategies. Our findings indicate that antibodies against specific adipokines could become a beneficial component of clinical breast cancer treatment in the future.Keywords: breast cancer, adipokines, tumor progression, adipose tissue, secretome

Abstract Circular RNAs (circRNAs) are widely involved in diverse biological processes of cancers. Nonetheless, the potential function of hsa_circ_0008305 in hepatocellular carcinoma (HCC) remains largely unknown. This study aims to elucidate the role and underlying mechanism of hsa_circ_0008305 in HCC. Our findings reveal that the novel circRNA hsa_circ_0008305 (circPTK2) is significantly upregulated in HCC tissues, with its elevated expression being positively correlated with advanced tumor T stage and vascular invasion. The circular characteristics and subcellular localization of hsa_circ_0008305 was determined by RNase R treatment and RNA nucleocytoplasmic separation. Further functional assays, including CCK8, EdU, colony formation assays, scratch-healing, transwell assays, and Xenograft tumor models were conducted to explore the biological functions of circPTK2. The regulatory mechanisms of circPTK2 were elucidated through RNA sequencing, enrichment analysis, and dual luciferase reporter assay. Our findings indicate that circPTK2 is stably localized in the cytoplasm. Functionally, circPKT2 promoted the HCC cells proliferation, migration, and invasion both in vitro and vivo. Mechanistically, circPTK2 was found to positively regulates the expression of AKR1C3 by acting as a sponge for miR-379-5p. Inhibition of miR-379-5p significantly mitigates the biological effects induced by circPTK2. AKR1C3 is identified as a direct target of miR-379-5p, and silencing AKR1C3 overturns the promotion progression effects of miR-379-5p inhibitor. In conclusion, our results revealed that circPTK2 facilitates the malignant progression of HCC via sponging miR-379-5p to up-regulate AKR1C3 expression.

Abstract Long non-coding RNAs (LncRNAs) are crucial regulators of gene expression and cellular processes, with significant implications for cancer research. This review focuses on the role of LncRNA CARMN (Cardiac Arrest and Regulated Myocyte Nuclear Protein) in various cancers. CARMN, originally identified for its function in cardiac tissues, has shown dysregulated expression in several tumor types, including cervical, breast, colorectal, and esophageal cancers. Its altered expression often correlates with tumor progression, metastasis, and patient prognosis, suggesting its potential as both a biomarker and therapeutic target. In cervical cancer, CARMN's role as a tumor suppressor is highlighted by its ability to inhibit cell proliferation, migration, and invasion through interaction with the miR-92a-3p/BTG2 axis and modulation of the Wnt/β-catenin signaling pathway. In breast cancer, CARMN acts as an enhancer RNA, affecting epithelial-mesenchymal transition and metastasis by regulating MMP2 via DHX9. The downregulation of CARMN in triple-negative breast cancer is associated with enhanced sensitivity to chemotherapy. In colorectal cancer, CARMN’s expression is regulated by m6A methylation and mutant p53, influencing tumor growth through miR-5683 and FGF2. Lastly, in esophageal cancer, genetic variations in CARMN affect cancer susceptibility, with certain SNPs and haplotypes associated with either increased or decreased risk. Additionally, the relationship between CARMN and immune cell dynamics highlights its potential role in cancer immune surveillance and therapy. Finally, we found that CARMN may regulate immune cell exhaustion in the tumor microenvironment by influencing the recruitment and activation of NK cells and T cells, as well as modulating macrophage polarization. This review emphasizes the diverse roles of CARMN across different cancers and its potential as a diagnostic and therapeutic tool. Future research should address the mechanistic details of CARMN’s involvement in cancer, validate its clinical utility, and explore its therapeutic potential in combination with existing treatments.

Background. Clinical diagnosis of papillary thyroid cancer usually occurs at the stage of tumor progression accompanied by intensive processes of growth, invasion, formation of blood vessels to provide blood supply to the tumor, the structure and quantitative changes of which can be more informatively accurately assessed by polarization biomedical optics. The purpose of the study was to substantiate the possibility of using polarization biomedical optics methods in the diagnosis of papillary thyroid cancer based on the principles of comprehensiveness and integrated pathophysiology. Materials and methods. Two groups of patients were stu­died: the control group — healthy donors (n = 51), the experimental group — patients with papillary thyroid cancer (n = 51) who underwent a puncture biopsy of the thyroid gland for diagnostic purposes using the fundamental idea of polarization biomedical optics with two analytical approaches — statistical and topographic (multifractal). Instrumental laser methods were used: polarization, interference, digital holographic. The statistical parameters of polarization azimuth maps, polarization azimuth of phase and multifractal spectra of digital microscopic images of native histological sections of thyroid biopsy from patients with papillary cancer were quantitatively evaluated with the determination of average, dispersion, asymmetry and excess. The significance of differences compared to the control, taken as 100 % was assessed using the Student’s parametric test (p

Abstract Background Sentrin/SUMO-specific protease 3 (SENP3) is essential to regulate protein stability and function in normal and cancer cells. Nevertheless, its role and action mechanisms in prostate cancer (PCa) remain elusive. Thus, clarification of SENP3’s involvement and the SUMOylation process in PCa is pivotal for discovering potential targets and understanding SUMOylation dynamics. Methods Cell viability, EdU staining, live cell imaging, and cell cycle assays were used to determine proliferation of PCa cells. Transwell and wound-healing assays were used to detect migration of PCa cells. The interaction between SENP3 and SIX1 was determined by co-immunoprecipitation, western blotting, and immunofluorescence assays. Xenograft models established on NOD-SCID mice were used to evaluate in vivo effects post SENP3 knockdown. Immunohistochemistry was performed to investigate the expression of SENP3 in PCa tissues. Results This study found that SENP3 is highly expressed in PCa cell lines and tissues from PCa patients. Overexpressed SENP3 is associated with metastatic malignancy in PCa. Various in vivo and in vitro experiments confirmed that SENP3 promotes the proliferation and migration of PCa. In addition, SENP3 interacts with the SD domain of SIX1 and mediates its deSUMOylation and protein stability. Lys154 (K154) is required for the SUMOylation of SIX1. More importantly, SENP3 promotes the malignancy of PCa through the regulation of SIX1. Conclusions We unravel the significant role of SENP3 in regulating protein stability of SIX1 and progression of PCa, which may deepen our understanding of the SUMOylation modification and provide a promising target for management of metastatic PCa.

A cancerous tumor in the brain known as glioblastoma multiforme (GBM) originates from astrocytes of the central nervous system. Consequently, GBM poses significant challenges to the oncology community because of its aggressive characteristics and poor prognosis. GBM hallmarks include fast growth, invasiveness, and high rates of recurrence. This tumor is highly heterogeneous with different genetic and molecular features found within the tumor cells. There is an ongoing obstacle to conceptualizing effective management for this grappling disease. This is largely due to the tumor displaying intra-heterogeneity, in addition to a plethora of differences in the tumor’s microenvironment. The heterogeneity exhibited by this tumor not only makes it more resistant to treatment but also influences its ability to evolve. The Epidermal Growth Factor Receptor (EGFR) which falls under the Human Epidermal Growth Factor (ErbB) family is a transmembrane receptor that assists in understanding complex molecular pathways involved in GBM formation. EGFR mutations have been shown to affect signaling cascades including Ras/Raf/MEK/ERK, PI3K/Akt/mTOR, JAK/STAT, PLC/PKC among others transforming cellular machinery involved in cell survival, proliferation and invasion. Knowledge about EGFR’s aberrant mutations can be useful for developing novel therapeutic strategies aimed at EGFR inhibition in GBM therapy. This gives hope for patients with this challenging disease to have better outcomes.

Purpose: Craniopharyngiomas (CPs) often lead to growth hormone deficiency (GHD) in children. Growth hormone replacement therapy (GHRT) is essential for managing GHD but its impact on body mass index (BMI) and metabolic outcomes is controversial. Concerns exist that GHRT might contribute to tumor recurrence, with guidelines varying on when to start therapy post-surgery. This updated systematic review and meta-analysis explores the effects and timing of GHRT in children post-craniopharyngioma surgery. Methods: We systematically searched PubMed, Embase, and Cochrane Library databases. Included studies compared the effects of GHRT in childhood-onset craniopharyngioma patients who received GHRT versus those who did not. Random-effects meta-analyses were used to pool relative risk (RR) or mean difference (MD) for each outcome. Heterogeneity was assessed using the I² statistic. This study is registered with PROSPERO (CRD42024498082). Results: We included 11 studies in the meta-analysis. No differences in tumor progression/recurrence were found between the GHRT and no GHRT groups (RR 0.77, 95% CI 0.56–1.05, p = 0.10). The impact of timing of GHRT is less clear because of limited data and high heterogeneity. There were no differences in BMI between the GHRT and no GHRT (MD -0.94, 95% CI -1.88,0.00, p = 0.05). Two studies reported that GHRT might improve lipid profiles. Conclusion: Our study suggests that GHRT does not increase the risk of tumor progression/recurrence in CP patients. GHRT can improve linear growth, but its effects on the BMI and lipid profiles remain inconclusive, requiring further studies. [ABSTRACT FROM AUTHOR]

ObjectiveTo explore the role of MAPK4 in cervical squamous cell carcinoma (CSCC) for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets. MethodsThe TCGA cohort was subjected to Kaplan-Meier survival analysis. Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis. A nomogram was constructed based on MAPK4 mRNA levels. Western blot, CCK-8, colony formation, and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC. DIA proteome sequencing was used to identify effector molecules regulated by MAPK4. Combined with the above cell function experiments, the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression. ResultsCSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis. The constructed nomogram based on MAPK4 can accurately predict the 1-, 3-, and 5-year survival rates of patients. Compared with that in normal cervical tissues, MAPK4 protein expression was up-regulated in tumors. MAPK4 knockdown substantially inhibited the proliferation, colony formation, migration, and invasion of CSCC ME180 and SiHa cells. SLC3A2 is a downstream effector molecule of MAPK4. Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation, colony formation, migration, and invasion. ConclusionMAPK4 is a candidate prognostic biomarker for patients with CSCC. MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression, making it a potential molecular therapeutic target for patients with CSCC.

Xin Yang,1,&ast; Lei Fan,2,&ast; Jicheng Huang,2 Yongjun Li1 1Peking University Fifth School of Clinical Medicine, Beijing, People’s Republic of China; 2Breast Center, Department of Thyroid-Breast-Hernia Surgery, Department of General Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongjun Li, Email liyongjun4679@126.comBackground: Timely detection of tumor progression in breast cancer (BC) patients is critical for therapeutic management and prognosis. Plasma exosomal miRNAs are potential liquid biopsy markers for monitoring tumor progression, but their roles in BC remain unclear.Methods: In the TCGA database, we first screened for miRNAs significantly associated with BC progression by comparing miRNA expression in para-carcinoma tissues, stage I BC tissues, and stage II–III BC tissues (n = 1026). Cox regression analyses and survival analyses were performed on candidate miRNAs to explore their prognostic value (n = 848). KEGG, GO, and PPI analyses were used to identify enriched pathways associated with cancer. Finally, the potential of candidate miRNAs as liquid biopsy markers was evaluated by sequencing and analyzing plasma exosomal miRNAs from our collection of 45 BC patients (14 in stage I, 31 in stage II–III) and 5 healthy controls, combined with qRT-PCR analysis to assess the correlation of candidate gene expression in plasma exosomes and BC tissues.Results: We found that only miR-203a-3p was progressively elevated with BC progression and was associated with poor prognosis in the TCGA dataset. Its potential target genes were enriched in pathways related to tumor progression, and the downregulation of 48 of these genes was associated with poor prognosis. More importantly, plasma exosomal miR-203a-3p was also found to gradually increase with BC progression, and its expression was positively correlated with miR-203a-3p in BC tissues. This result suggests that plasma exosomal miR-203a-3p may reflect the expression of miR-203a-3p in tumor tissues and serve as a potential liquid biopsy marker for monitoring BC progressions.Conclusion: We found for the first time that elevated miR-203a-3p was associated with BC progression and poor prognosis. Our findings suggested that plasma exosomal miR-203a-3p could hold potential as a liquid biopsy marker for evaluating BC progression in patients.Keywords: plasma exosomal miR-203a-3p, breast cancer, tumor progression, liquid biopsy marker

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Dendritic cells (DCs) constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses. As a crucial component of the immune system, DCs have a pivotal role in the pathogenesis and clinical treatment of CRC. DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response. However, the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment. This review systematically elucidates the specific characteristics and functions of different DC subsets, as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment. Moreover, how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed, which will provide new perspectives and approaches for immunotherapy in patients with CRC.

Abstract Background Chondroitin polymerizing factor (CHPF) has been found to be involved in the development of numerous cancers and correlated with poor prognosis. However, its role in the tumorigenesis and development of colorectal cancer (CRC) remains unknown. Methods In our research, we explored CHPF expression and clinicopathological characteristics using The Cancer Genome Atlas Program (TCGA), UALCAN, GSE9348, TIMER2.0 and The Human Protein Atlas (HPA) database, in addition, we validated CHPF expression in CRC cell lines by Real-Time Quantitative PCR (qRT-PCR) and Western blot (WB). KM-Plotter, PrognoScan and TCGA were also utilized to verify its prognosis value in CRC. Small-interfer RNA (Si-RNA) was used to perform Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2′-deoxyuridine (EDU), transwell and wound healing assays to testify its function on the tumor progression. Based on TCGA database, we probed potential biological mechanism by which CHPF play its role via clusterProfiler package and GEPIA database and we validated their correlation by WB assay. Moreover, we explored its potential association with the tumor microenvironment (TME), immune infiltrated cells, immune checkpoints, tumor mutation burden (TMB) as well as microsatellite instability (MSI), and investigated immunotherapy sensitivity via Tumor Immune Dysfunction and Exclusion (TIDE) algorithm as well as potentially effective therapeutic drugs via pRRophetic algorithm. Results CHPF was identified upregulated in CRC tissues and cells, correlated with poor prognosis, and nodal metastasis status, stage and histological subtype. Down-regulation of CHPF inhibited CRC cell proliferation, migration and its expression correlated with wnt pathway key molecules. In addition, high expression of CHPF was positively correlated with TME scores, Regulatory T cells (Tregs) cell infiltration degree, Programmed death-1 (PD-1), MSI-high (MSI-H), and TIDE scores, however, not with TMB. Targeted drug analysis showed that patients with high CHPF expression were more sensitive to telatinib, recaparib, serdemetan, and trametinib. Conclusion CHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy.