Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a multifunctional protein belonging to the heterogeneous nuclear ribonucleoprotein family. The K‑homology domain is the most evolutionarily conserved feature of hnRNPK and is responsible for RNA‑binding. hnRNPK interacts with both chromatin and RNA in numerous species. Initially characterized as an RNA‑binding protein, hnRNPK functions as a structural protein, integrating a number of signaling pathways and participating in gene expression regulation, RNA processing, cell cycle control and apoptosis. hnRNPK exhibits aberrant expression in numerous tumors, functioning paradoxically as either an oncogene or tumor suppressor depending on cellular context, expression levels and post‑translational modifications. Recent advancements have outlined the involvement of hnRNPK in tumor cell migration, angiogenesis and chemoresistance through interactions with long non‑coding RNAs and the regulation of key signaling pathways. The present review summarizes current knowledge regarding the structure, function and clinical importance of the hnRNPK in cancer, highlighting its potential as both a biomarker and therapeutic target.

Among pituitary adenomas, prolactin‑secreting pituitary neuroendocrine tumours (PRL‑PitNETs) are unique in that pharmacotherapy, specifically cabergoline (CAB), can be used as a first‑line treatment, and it is the recommended therapeutic option. However, the mechanisms underlying CAB resistance remain incompletely understood. In the present study, gene microarray analysis and clinical tissue specimens were used to identify circular RNAs (circRNAs) associated with CAB resistance. circOMA1 expression was quantified in PRL‑PitNET tissues and patient plasma using reverse transcription‑quantitative PCR, and its diagnostic potential was evaluated in 219 patients with pituitary adenoma. Gain‑ and loss‑of‑function assays, combined with molecular biology techniques, were used to investigate the biological function of circOMA1 and the underlying molecular mechanism. circOMA1 was identified as a critical circular RNA influencing CAB resistance and prognosis in PRL‑PitNET. Mechanistically, circOMA1 acted as a miR‑145‑5p sponge, leading to upregulation of the E3 ubiquitin ligase Kelch‑repeat and BTB domain‑containing protein 7. This promoted ubiquitination of the CAB‑specific, high‑affinity G‑protein‑coupled receptor dopamine D2 receptor. Consequently, downstream autophagy was attenuated, and AKT pathway inhibition was impaired, which underlied the resistance. Furthermore, in vitro and in vivo studies demonstrated that circOMA1 was transported via exosomes, facilitating the transmission of CAB resistance among PRL‑PitNET cells. Plasma exosomal circOMA1 levels were significantly elevated in PRL‑PitNET patients preoperatively. These findings established circOMA1 as a key mediator of CAB resistance and a potential prognostic indicator in patients with a PRL‑PitNET.

Bladder cancer is a challenging disease with high recurrence rates and limited treatment options. Studies have highlighted the role of ferroptosis, an iron‑dependent cell death mechanism, in cancer progression and treatment. In the present study, the regulatory mechanisms of polyphyllin II (PPII) on ferroptosis in bladder cancer cells were investigated. Cell viability and colony formation assays demonstrated that PPII effectively inhibited the proliferation of bladder cancer cells. RNA sequencing analysis revealed differentially expressed genes upon PPII treatment, with Cluster 6 exhibiting dose‑dependent expression changes. Gene Ontology and pathway enrichment analyses revealed enrichment of ferroptosis‑related pathways. PPII treatment markedly increased reactive oxygen species (ROS) levels and promoted Fe²+ accumulation in bladder cancer cells. Additionally, PPII downregulated the expression of glutathione peroxidase 4 (GPX4), a key regulator of ferroptosis. These findings indicate that PPII promotes ferroptosis in bladder cancer cells through the modulation of ROS levels and GPX4 activity. Further investigations into the molecular mechanisms and potential combination therapies are warranted.

Drug therapy serves a key role in the treatment of cervical cancer, which is one of the most common types of solid tumor in female patients. Therefore, it is important to seek more effective and less toxic therapies. Protein arginine methyltransferase 5 (PRMT5) is a key oncogenic target in cervical cancer, providing a rational basis for the development of targeted therapeutic agents. MS4322 is a highly selective proteolysis targeting chimera degrader specifically targeting PRMT5. Therefore, the present study aimed to investigate the therapeutic potential of MS4322 against cervical cancer and the underlying molecular mechanisms. The effects of MS4322 on human cervical HeLa cells were investigated by Cell Counting Kit‑8, clone formation, wound healing and Transwell assay, flow cytometry, immunofluorescence staining, immunohistochemistry and small interfering RNA assay. PRMT5 expression was upregulated in cervical cancer tissue, and functional analyses confirmed that PRMT5 promoted the proliferation of cervical cancer cells. MS4322 significantly decreased PRMT5 mRNA expression, as well as the proliferation, migration, invasion and clone formation ability of HeLa cells, leading to cell cycle arrest in G0/G1 phase and inducing apoptosis. Mechanistically, MS4322 downregulated the expression of PRMT5, β‑catenin, Wnt‑3a, and c‑myc, while upregulating GSK‑3β, thereby inactivating the Wnt/β‑catenin pathway. These findings indicated that MS4322 exerted anti‑tumor effects via regulating the PRMT5/Wnt/β‑catenin pathway and may serve as a promising candidate agent for cervical cancer treatment.

Ubiquitination is crucial for regulating diverse cellular functions, including protein degradation, cell cycle progression, signal transduction and gene expression. This intricate process is mediated by the ubiquitin proteasome system. Within this system, ubiquitin‑specific protease 10 (USP10) is a key member that, through its deubiquitinase activity, orchestrates multiple cellular processes, such as DNA damage repair, immune and inflammatory responses, environmental adaptation and autophagy. The biological activity and protein stability of USP10 are extensively regulated by post‑translational modifications, including PARylation, histone methylation and ubiquitination. Functionally, USP10 has a dual role in tumorigenesis: It can either promote or suppress cancer progression and metastasis by influencing oncogenic signaling pathways. Beyond cancer, USP10 has been implicated in the pathogenesis of cardiovascular and neurodegenerative diseases, as well as organ fibrosis, underscoring its broad physiological relevance. Decades of research have spurred the development of a range of USP10 inhibitors, such as Spautin‑1, P22077, HBX19818, Wu‑5 and D1. The present review provides a comprehensive overview of recent advances in understanding the role of USP10 in maintaining homeostasis and dissects the pathological mechanisms in human diseases. The review further highlights the potential of precise USP10‑targeted interventions as promising therapeutic strategies for disease prevention and treatment.

MicroRNAs (miRNAs or miRs) are a class of small non‑coding RNAs that are critical regulators of gene expression. By targeting messenger RNAs, they play essential roles in various biological processes, including development, differentiation, immunity, metabolism and apoptosis. miRNA dysregulation is often associated with tumorigenesis and cancer progression. miR‑124, a miRNA predominantly and specifically expressed in the central nervous system, is commonly downregulated in various cancers. It inhibits multiple malignant traits, including tumor growth, metastasis, stemness and chemoresistance. Furthermore, miR‑124 influences the tumor microenvironment and modulates antitumor immune responses. These diverse functions highlight their significant potential for clinical application. Its expression is modulated by various upstream factors, including transcription factors, signaling pathways, epigenetic modifications, and other non‑coding RNAs. However, the precise mechanisms governing this upstream regulation require further investigation. Despite this, the translational application of miR‑124 for early cancer diagnosis and therapy faces several significant challenges, including improving its stability and bioavailability and developing effective in vivo delivery systems. The present study provides a comprehensive overview of the multifaceted roles of miR‑124 in cancer, elucidating its underlying molecular mechanisms and exploring its clinical potential. By synthesizing the current literature, it was aimed to consolidate the current understanding of miR‑124 and identify promising avenues for future research.

The molecular classification of endometrial carcinomas (ECs) is now integrated into clinical practice. However, identification of polymerase-ε (POLE) variants remains reliant on DNA sequencing, which limits broader implementation. Given the strong prognostic value of pathogenic POLE mutations and the established efficacy of immunohistochemistry (IHC) for detecting mismatch repair (MMR) deficiency and p53 abnormalities, there is a clear need for IHC-based screening strategies to identify patients likely to carry POLE variants and prioritize them for confirmatory sequencing. In this study, we analyzed 24 cases with POLE pathogenic mutations (POLEmut ECs), 3 with benign POLE variants, and 32 matched cases with no specific molecular profile (NSMP) from a cohort of 378 ECs. IHC evaluation of the ataxia telangiectasia mutated (ATM) protein revealed that POLE-mutated ECs (with pathogenic or benign POLE variants) exhibited significantly higher frequencies of non-diffuse positive staining patterns, including null, heterogeneous positive, and subclonal loss, compared with NSMP cases. Targeted next-generation sequencing of all exons across 474 cancer-related genes in the 27 POLE-mutated ECs and 20 NSMP cases with ATM non-diffuse positive staining patterns confirmed that POLE-mutated ECs typically had high tumor mutational burden and were enriched for ATM truncating variants. ATM molecular alterations, including various variant subtypes and multisite mutations, also closely correlated with these staining patterns. Based on these findings, we refined the ATM IHC interpretation framework to integrate staining patterns with sequencing data for improved molecular correlation. Specifically, the null and subclonal loss patterns showed high specificity (96.9%), positive predictive value (94.1%), and accuracy (79.7%) for identifying POLE variants. Notably, the null pattern appeared exclusively in ECs with pathogenic POLE mutations. These results suggest that ATM IHC staining is an effective screening tool for identifying patients who may benefit from confirmatory POLE sequencing among those lacking MMR deficiency or p53 abnormalities.

CD8+ T cell exhaustion represents a major obstacle to effective cancer immunotherapy. While stem-like progenitor exhausted T (TPEX) cells can differentiate into intermediate (Int-TEX) and terminally exhausted (TEX) subsets, the epigenetic regulation of this process is unclear. We identify the RNA methyltransferase Mettl8 as a critical regulator, with expression significantly higher in TPEX than in TEX subsets. In anti-PD-1 responding non-small cell lung cancer patients, Mettl8 and the stemness factor TCF7 were downregulated. In murine models, Mettl8 deletion restrained tumor progression by driving TPEX differentiation into effective Int-TEX cells. Mechanistically, Mettl8 stabilizes Tcf7 mRNA via m3C modification and enhances Tcf1 protein expression. Additionally, Mettl8 interacts with Tcf1 to facilitate chromatin looping at the Tox locus, maintaining TPEX stemness. Pharmacological Mettl8 inhibition promoted TPEX-to-Int-TEX differentiation and tumor control. Combining this inhibition with anti-PD-1 therapy yielded synergistic efficacy. Our findings establish Mettl8 as a pivotal regulator of TPEX fate and a promising therapeutic target for enhancing immunotherapy.

Refractory chylothorax following oesophagectomy is a challenging complication, often requiring surgical re-intervention. We describe a standardized technique for thoracic duct ligation using indocyanine green (ICG) fluorescence guidance. A 62-year-old male presented with high-output chylothorax 40 days after a minimally invasive Ivor Lewis oesophagectomy, refractory to conservative management. The procedure involved pre-operative bilateral inguinal lymph node injection of ICG. A right-sided three-port VATS approach was utilized. Intra-operatively, a provocative fatty meal test (cream and olive oil) was administered via the nasogastric tube. Using near-infrared fluorescence, the thoracic duct was rapidly identified. The technique included meticulous dissection, mass ligation with silk sutures, and reinforcement with polymer clips. Chemical pleurodesis with talc was added to ensure pleural symphysis. The patient was discharged on post-operative Day 5 with no recurrence at 30-day follow-up. This video tutorial demonstrates that ICG-guided VATS ligation, combined with inguinal lymph node injection, provides a safe, reproducible, and highly effective strategy for managing complex post-oesophagectomy chylothorax.

Byakangelicol (BYA) belongs to coumarins, which have anti-inflammatory and anti-tumor pharmacological properties, but its inhibitory effect on liver cancer and its mechanism are still indistinct. This study explored the mechanism of action by which BYA affects hepatocellular carcinoma (HCC). Cell cytotoxic and apoptosis assay results showed that BYA effectively killed three kinds of HCC cells and induced mitochondrial pathway apoptosis of HepG2 cells. Furthermore, the results of network pharmacological analysis, flow cytometry and western blot assays demonstrated that BYA can induced reactive oxygen species (ROS) accumulation, which in turn upregulated the phosphorylation expression of JNK and p38 while downregulating the phosphorylation expression of AKT, ERK, and STAT3. Meanwhile, the expression of these proteins was reversed after MAPK inhibitors pretreatment. Cell cycle and cell metastasis assay results showed that BYA can induce G2/M phase arrest and inhibit cell metastasis. At the same time, the expression of related proteins was reversed after ROS inhibitors (N-Acetyl-l-cysteine) pretreatment. The research results reveal that BYA can cause the accumulation of ROS within cells, and induce apoptosis in HepG2 cells through the mitochondrial pathway, thereby leading to cell cycle arrest at the G2/M phase and inhibition of cell migration ability. This study provides theoretical support for the clinical application of BYA in the treatment of HCC.