High mobility group box 3 (HMGB3) acts as an essential participator in fundamental biological processes, including transcriptional regulation, chromatin remodeling and DNA repair. HMGB3 is highly expressed and functionally essential during embryonic development, particularly in the hematopoietic and nervous systems, but it is significantly downregulated or silenced in most normal adult tissues. Its aberrant upregulation has been revealed in numerous human malignancies, such as leukemia, as well as breast, bladder, colorectal and gastric cancer, and its expression levels have been established to be closely associated with poor prognosis of specific patients. Accordingly, the present review systematically explores the central roles of HMGB3 in mediating resistance to cancer therapy. This review focuses on its multifaceted mechanisms of maintaining cancer stemness, enhancing DNA damage repair, modulating cell death pathways and remodeling the tumor microenvironment, thereby contributing to the resistance to chemotherapy, radiotherapy, targeted therapy and immunotherapy collectively. HMGB3 can be accepted as a key target in the development of highly promising therapeutic strategies, given its pivotal involvement in multidrug resistance, which may offer novel avenues for overcoming clinical treatment resistance and improving patient outcomes.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the paraffin‑embedded glioma tissue sections shown in Fig. 2A on p. 494, the Ki‑67/Grade III and DTX3L/Grade IV data panels contained an overlapping section, suggesting that these data panels were derived from the same original source where different experimental groups were reported. In addition, GAPDH control western blots featured in Figs. 1C and 4E were found to be strikingly similar, even though the experimental conditions reported for these figure parts were different. The authors have been contacted by the Editorial Office to offer an explanation for these apparent anomalies in the presentation of the data in their paper, and we are awaiting their response. Due to the fact that we have been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of these potential problems while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 40: 491‑498, 2017; DOI: 10.3892/ijmm.2017.3023].

Nasopharyngeal carcinoma, a malignancy associated with Epstein‑Barr virus, presents a complex immune editing landscape in which T cell fate determination carries out a central role. T cell metabolic exhaustion, Epstein‑Barr virus antigen presentation and tertiary lymphoid structure remodeling are important in the context of tumor immune evasion. Although individual mechanisms have been extensively studied, their interplay and collective contribution to immune editing remain incompletely understood. The present review summarizes the current advances in nasopharyngeal carcinoma immune editing, with a focus on the molecular network underlying T cell fate decisions. How these mechanisms can be leveraged to develop novel immunotherapeutic strategies is further discussed. By integrating recent findings, the present review aims to offer new insights into the intricate immune landscape of nasopharyngeal carcinoma and to provide a theoretical basis for improving immunotherapy efficacy.

Chromodomain helicase DNA‑binding protein 4 (CHD4) is a core adenosine triphosphate (ATP)‑dependent chromatin‑remodeling factor of the nucleosome‑remodeling and deacetylase (NuRD) complex. It plays a crucial role in chromatin structure regulation, gene expression regulation, and DNA damage response. It has been demonstrated that CHD4 has context‑dependent functions in tumor development and progression. It can influence tumor progression via such mechanisms as regulating tumor‑related signaling pathways, maintaining the silencing of tumor suppressor genes, and promoting metabolic adaptation; it can also exert tumor‑suppressive effects in specific transcriptional regulatory environments. Additionally, during DNA damage response, CHD4 participates in chromatin remodeling at damage sites, in cell cycle recovery, and in repair pathway selection. It is also involved in the development of tumor treatment resistance through mechanisms that include regulation of DNA repair, cell cycle progression, drug efflux, the tumor immune microenvironment, and replication fork stability. It has also been shown that various non‑coding RNAs participate in the functional regulation of CHD4 by modulating its expression, localization, and protein stability. In summary, as a key node connecting chromatin regulation, genome stability, and tumor treatment response, CHD4 holds significant importance in tumor progression and treatment.

Pituitary tumors, as common intracranial neoplasms, present challenges in clinical management because of high postoperative recurrence rate, drug resistance and pronounced side effects. Astragaloside IV (AS‑IV), the primary active component of the traditional Chinese herb Astragalus membranaceus, has antitumor activity in numerous types of cancer. However, its effects and mechanisms in pituitary tumors remain unclear. The present study aimed to investigate the effects of AS‑IV on proliferation and apoptosis of pituitary tumor cells and to elucidate its molecular mechanisms. Cell Counting Kit‑8 (CCK‑8), TUNEL, EdU, immunohistochemistry (IHC), and Western blotting, among others, showed that AS‑IV significantly suppressed the viability of the rat pituitary tumor cell lines GH3 and MMQ in a concentration‑ and time‑dependent manner while inducing apoptosis. Tubulin β4B Class IVb (TUBB4B) was highly expressed in pituitary tumor tissue and its overexpression promoted cell proliferation while inhibiting apoptosis. AS‑IV bound TUBB4B with high affinity, forming a stable complex. TUBB4B regulation influenced pituitary tumor cell sensitivity to AS‑IV, with AS‑IV demonstrating enhanced antitumor efficacy in TUBB4B‑overexpressing tumors. TUBB4B activated the ERK/MAPK signaling pathway by upregulating Stathmin 1 (STMN1) expression, which promoted G1/S phase transition. The ERK‑specific inhibitor U0126 reversed this pro-proliferative effect. To the best of our knowledge, the present study is the first to reveal that AS‑IV inhibits pituitary tumor proliferation and promotes apoptosis by targeting TUBB4B to regulate the STMN1‑ERK signaling axis, providing a novel theoretical basis and potential strategies for traditional Chinese medicine treatment and molecular targeted research on pituitary tumors.

The global incidence of thyroid cancer (TC) has markedly increased in recent years, making it the most prevalent endocrine‑related cancer worldwide. TC primarily originates from follicular and parafollicular cells of the thyroid gland, and includes four main pathological types: Papillary TC (PTC), follicular TC, medullary TC (MTC) and anaplastic TC. Notably, characteristic oncogenes and tumor suppressor genes are associated with TC, which are considered targets for the development of treatment strategies. The rearranged during transfection (RET) gene serves a pivotal role in the development of TC, and mutations and fusions of this gene are closely associated with the onset of MTC and PTC. The structure of RET includes four cadherin‑like domains and 16 cysteine residues in its extracellular domain, which confer unique functionalities and contribute to its intracellular role. RET activation is a complex process involving multiple intracellular events, including calcium ion binding, glial cell line‑derived neurotrophic factor family ligand binding, and RET receptor aggregation, dimerization and autophosphorylation. The present study reviews the structure and function of the RET proto‑oncogene and its pathogenic roles in various TC subtypes.

RNA polymerase II (Pol II) is an essential eukaryotic enzyme that transcribes protein‑coding genes and various non‑coding RNAs. RNA polymerase II, I and III subunit L (POLR2L) is a highly conserved component shared by RNA polymerase subunits I, II, and III, which contributes to transcriptional regulation, enzymatic structural integrity, key cellular processes such as proliferation, differentiation, and stress responses. Recent research has shown that POLR2L is not merely a Pol II structural subunit but also plays key roles in disease progression, particularly cancer, where POLR2L dysregulation contributes to tumor growth, metastasis, and resistance to chemotherapy. Additionally, POLR2L is closely linked to major signaling pathways including the PI3K‑Akt, Wnt/β‑catenin, and TGF‑β pathways, highlighting the diverse roles played by POLR2L in cellular signaling. This review summarizes current knowledge on the structural and functional properties of POLR2L, its involvement in various diseases, and its potential as a therapeutic target. By outlining the diagnostic and therapeutic relevance of POLR2L, this review aims to provide a framework for understanding how POLR2L related research may inform transcriptional regulation and its impact on human health and disease.

Histone modification is an important mechanism of epigenetic regulation. New histone modifications play key roles in the regulation of gene expression and in the development and progression of various diseases. In addition to histone modifications, epigenetic regulation includes classic pathways such as DNA methylation, chromatin remodeling complexes and non‑coding RNAs, which interact with each other and jointly shape the occurrence and development of gastric cancer (GC). The present study systematically elaborated on the role of histone modification in GC and introduced several main types of histone modification, including acetylation, methylation, citrullination, ubiquitination and lactylation, focusing on histone lactylation modification and exploring its biochemical basis, interaction with other modifications and functions such as metabolic reprogramming, cell proliferation, migration and immune escape, covering non‑tumor and other cancer fields. On this basis, the specific application of histone modification (acetylation, methylation and other modifications) in GC is further explained and the effects of histone lactylation on metabolic reprogramming, proliferation, migration and immune escape of GC are analyzed in detail. Finally, the clinical significance of histone lactylation modifications in the diagnosis and prognosis of GC, biomarkers, therapeutic targets and drug resistance mechanisms provides a reference for an in‑depth understanding of the role of histone modifications, especially lactylation modifications, in the development of GC and clinical transformation applications.

Lung cancer is an aggressive malignancy associated with a rapid progression and poor prognosis, for which immunotherapy only exhibits modest efficacy in most patients. In lung cancer, high lactate is associated with a low immunotherapy response and shortened survival; however, causal lactylation‑related genes remain to be elucidated. In the present study, candidate genes were screened using Mendelian randomization (MR) analysis, with expression quantitative trait loci data and genome‑wide association study summary statistics used as analytical resources. A total of 46 lactylation‑related genes were included in the MR analysis, and multiple testing correction was performed using the false discovery rate (FDR) and Bonferroni methods to control the false‑positive risk. MR identified three core genes [platelet‑type phosphofructokinase; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; and stathmin 1 (STMN1)]. Among these genes, only STMN1 was significantly associated with increased lung cancer risk (inverse variance weighting original P=0.005, FDR‑corrected P=0.014995, Bonferroni‑corrected P=0.014995, odds ratio=1.741, 95% confidence interval: 1.182‑2.564), with robust results confirmed by heterogeneity/pleiotropy/sensitivity analyses. Subsequently, transcriptomic analysis was conducted to assess STMN1 expression in lung cancer tissues and its association with patient survival. In vitro (cell proliferation, migration, invasion and apoptosis assays) and in vivo experiments (murine tumor models) were also conducted to explore the function of STMN1. STMN1 exhibited upregulation in lung cancer tissues, and was associated with a shorter survival, reduced antitumor immune cell infiltration and an immunosuppressive tumor microenvironment (TME) phenotype. STMN1 knockdown inhibited lung cancer malignancy both in vitro and in vivo, and modulated key markers, whereas its overexpression exhibited the opposite effects. Additionally, STMN1 promoted global histone lactylation and histone H3 lysine 18 lactylation in lung cancer cells, establishing a direct functional link between STMN1 and the lactylation pathway. In conclusion, STMN1 is a lactylation‑related causal oncogene in lung cancer, driving progression via malignant phenotypes, and its high expression is associated with an immunosuppressive TME that may synergistically facilitate tumor progression. Therefore, STMN1 may be considered a novel target for lung cancer therapy.

Metastasis of hepatocellular carcinoma (HCC) is a key factor contributing to poor patient prognosis, with extracellular vesicles (EVs) and circulating tumor cells (CTCs) playing a marked synergistic role in this process. Current research suggests that EVs, acting as essential mediators of intercellular communication, facilitate CTC‑driven HCC recurrence and metastasis by transporting bioactive molecules, including nucleic acids, proteins and lipids. CTCs are regarded as the initiators of tumor metastasis, while the bioactive cargo carried by EVs functions as critical factors that promote their outgrowth. EVs not only remodel the microenvironment of target organs by forming a 'pre‑metastatic niche', but also establish a permissive microenvironment for CTC colonization. This tripartite interplay establishes a cascade model that enhances metastatic dissemination. The present manuscript reviewed the recent advancements and clinical value in understanding the roles of EVs and CTCs in HCC metastasis and recurrence, as well as the mechanisms by which EVs mediate CTC‑driven liver cancer spread, aiming to promote further in‑depth research into HCC metastasis mechanisms.

Objective To investigate the concordance of programmed death ligand-1 (PD-L1) expression between primary non-small cell lung cancer (NSCLC) and paired brain metastasis, analyze its relationship with clinicopathological characteristics, and evaluate the feasibility of using primary tumor PD-L1 status to predict brain metastasis status. Methods Thirty-two paired primary NSCLC and brain metastasis samples, pathologically diagnosed between January 1, 2017 and July 1, 2022, were collected. PD-L1 expression was detected by immunohistochemistry and interpreted using the Tumor Proportion Score (TPS), with cut-off values set at 1% and 50%. The Chi-square test was used to analyze the relationship between PD-L1 expression and clinicopathological features. Paired Chi-square and Kappa consistency tests were employed to assess the concordance of PD-L1 expression between primary and metastatic sites. Results PD-L1 expression showed no significant correlation with patient gender, age, treatment history, or histologic type. At the 1% cut-off, the overall PD-L1 expression showed moderate concordance between primary and metastatic sites (Kappa=0.624). Subgroup analysis revealed high concordance in untreated patients (Kappa=0.761, P=0.001), whereas the treated group showed weak concordance without statistical significance (Kappa=0.324, P=0.205). At the 50% cut-off, both the treatment group and the untreated group showed weak concordance without statistical significance. Although the chemotherapy subgroup showed perfect agreement (Kappa=1.000) at the 50% cut-off, the high-expression concordance rate was only 20.00%, indicating limited clinical reference value. Conclusion The strong concordance of PD-L1 expression in the untreated group patients supports the use of primary tumor PD-L1 status to guide clinical decision-making when brain metastasis tissue is unavailable. Treatment status (mainly including chemotherapy) may be an important factor affecting the consistency of high PD-L1 expression between primary NSCLC and brain metastasis.

Olfactory meningiomas are common neoplasms accounting for 4.5-18% of all intracranial meningiomas. Currently, transcranial (pterional, unilateral subfrontal, bilateral subfrontal, interhemispheric and through the frontal sinus) and endoscopic endonasal approaches are actively used.

Endocrine inactive pituitary microadenomas are ones of the most common incidental findings in neuroimaging. Their prevalence is up to tens of cases per 100.000. According to current data, the vast majority of microadenomas remain stable over long-term follow-up, and the risk of progression, hypopituitarism, or the need for surgical intervention is extremely low. Clinical factors such as baseline adenoma size, gender and age have not proven predictive value for the risk of microadenoma growth. Current recommendations for follow-up vary significantly. There is evidence of safety of less aggressive strategies (delaying the first MRI for up to 3 years without clinical manifestations and no routine hormonal screening in patients with stable course). This approach combines clinical effectiveness and cost-effectiveness. Thus, current data allow us to consider endocrine inactive pituitary microadenomas as lesions with favorable prognosis. Revising international guidelines in favor of more rational and personalized surveillance strategies appears to be a justified and necessary step to optimize clinical practice.

Dopamine agonists are an effective and safe treatment for prolactinomas. However, analysis of recent data has shown that dopamine agonists, including cabergoline, can cause tumor fibrosis and complicate subsequent surgery.

Background. Diffuse brainstem tumors account for 10-20% of all brain tumors in children. These neoplasms are the leading cause of death in pediatric neuro-oncology. There are no effective treatments for this disease. Overall survival rarely exceeds 1.5-2 years.

Glioblastoma or grade IV glioma is characterized by extremely poor prognosis. Resistance to radio- / chemotherapy and recurrences are associated with tumor stem cells. Transmembrane protein CD133 is considered a potential marker of tumor stem cells. To overcome the limitations of detecting cellular CD133 by antibodies, potential of aptamers (nucleic acid-based molecular recognition elements) is being explored. To obtain reproducible results, it is necessary to study the interaction of fluorescent aptamers to CD133 with standard cell lines and cell cultures derived from patient tumors using various methods.

Bladder cancer (BCa) progression is closely linked to the immune microenvironment. However, the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood. This study aims to identify a key molecule and elucidate its mechanisms, providing a theoretical basis for identifying novel therapeutic targets.

ADP-ribosyltransferases (ARTs) regulate key processes in cancer, including DNA repair, transcription, immune responses, and treatment resistance. The clostridial toxin-like ADP-ribosyltransferase (ARTC) family and the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family play a crucial role in genomic stability by modification of proteins either with mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). These ARTs are promising therapeutic targets and could serve as biomarkers in cancer management. This review explores the roles of these enzymes and current knowledge on specific inhibitors. A literature search was conducted in PubMed and Google Scholar to identify studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer. Among ARTC family, ART1 and ART3 modulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, influencing angiogenesis, tumor growth, and immune evasion via cluster of differentiation 8+ (CD8+) T-cell apoptosis. Within the ARTD family, poly(ADP-ribose)polymerase (PARP)1 and PARP2 are activated by DNA single-strand breaks and are clinically validated targets in cancers with homologous recombination deficiency, such as breast cancer susceptibility genes 1/2 (BRCA1/2)-mutated breast cancer. Their inhibition exemplifies synthetic lethality and has shown clinical efficacy. Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

The progression of prostate cancer cells to metastasis is supported by their tumor microenvironment. Within this microenvironment, infiltrating immune cells, such as B cells, can be either anti-tumorigenic or pro-tumorigenic. Our preliminary data showed that a higher density of the infiltrating B cells was found near prostate cancer cells in human cancer tissues, as compared to the benign prostate tissue regions, thus suggesting that infiltrating B cells would promote the progression of prostate cancer cells. In this study, we aim to investigate the role of infiltrating B cells in enhancing the migratory ability of human prostate cancer cells.

Long non-coding RNAs have been found to play a pivotal role in breast cancer, yet the majority of these lncRNAs remain to be thoroughly investigated. This study aimed to explore the role of differentially expressed long non-coding RNAs (lncRNAs) in breast cancer stemness and drug sensitivity.