This study aims to investigate the prognostic significance and potential biological functions of the MTORC1 signaling pathway-associated gene POLR3G in Hepatocellular carcinoma (HCC). A prognostic risk model for HCC was developed by integrating HCC-related datasets and associated clinical data obtained from The Cancer Genome Atlas (TCGA) database. The GSVA website was employed to analyze the model genes across pan-cancer datasets, focusing on copy number variations (CNV), single nucleotide variations (SNV), methylation differences, drug sensitivity and immune cell infiltration profiles. Subsequently, we examined the expression levels and prognostic significance of POLR3G in HCC. Utilizing Spearman correlation analysis, we identified genes associated with POLR3G. Furthermore, Gene Set Enrichment Analysis (GSEA) was employed to elucidate the potential signaling pathways in which POLR3G may be involved. The relationship between POLR3G expression and immune cell abundance in HCC samples was assessed using the ssGSEA algorithm. Finally, the impact of POLR3G on HCC cell proliferation was validated through CCK-8 and EDU cell proliferation assays. Through univariate Cox regression analysis and LASSO regression analysis, we established a prognostic risk model for HCC comprising 13 genes. The analysis revealed that individuals categorized in the low-risk group had a markedly improved overall survival probability relative to those in the high-risk group. POLR3G exhibited a markedly elevated expression in HCC tissues when compared to adjacent normal tissues. The expression of POLR3G was correlated with tumor grade, and elevated POLR3G expression was associated with poor prognosis in HCC patients. Furthermore, the expression level of POLR3G was found to be correlated with the level of immune cell infiltration. Knockdown of POLR3G significantly inhibited the proliferative capacity of hepatocellular carcinoma cells. The findings suggest that POLR3G may serve as a potential biomarker influencing the prognosis of hepatocellular carcinoma patients by modulating the tumor immune microenvironment.

Hepatoblastoma is the most prevalent liver cancer in children. Immunotherapy targeting immune checkpoint molecules has become pivotal in various cancer treatments. However, the clinical significance of immune checkpoint ligands in hepatoblastoma remains largely unclear due to various challenges. This study sought to first characterize the expression profile of the immune checkpoint ligand CD276 in hepatoblastoma and assess its potential as a predictor of malignant characteristics and regulator of neutrophil infiltration.

Neutrophils infiltrate lung tumours and can exhibit an immunosuppressive phenotype that promotes tumour growth, yet their regulation in early-stage lung cancer remains unclear. This study investigates molecular regulators of neutrophils in early-stage lung adenocarcinoma (LUAD) using publicly available gene expression datasets. An early-stage LUAD dataset (GSE31210) was analysed using CIBERSORTx to estimate neutrophil abundance. Weighted gene co-expression network analysis (WGCNA) identified the hub gene most correlated with neutrophil scores. Single-cell RNA sequencing (scRNA-seq) was used to determine the cellular source and regulatory mechanisms of this gene. A high neutrophil score was a negative prognostic factor, validated in independent datasets. WGCNA identified C1QA as the key gene linked to neutrophil abundance. scRNA-seq and immunofluorescence staining confirmed macrophages as the primary source of C1QA. Cell-cell communication analysis suggested C1QA interacts with neutrophils via complement receptors, contributing to an immunosuppressive tumour microenvironment. RT-qPCR showed C1QA expression correlated with IL-10 and TGFB1, markers of immunosuppression. C1QA is a poor prognostic marker in LUAD, potentially driving immunosuppressive tumour-associated neutrophils. Targeting C1QA and its pathway may offer a novel therapeutic strategy in early-stage LUAD.

According to GLOBOCAN 2022 cancer incidence and mortality statistics compiled by the International Agency for Research on Cancer, the incidence rate of breast cancer (BC) ranks second among all 36 types of cancers, just after lung cancer. Despite great advances in breast cancer (BC) treatment-including agents such as Tamoxifen, Fulvestrant, Toremifene, and Raloxifene, all of which are approved for the systemic treatment of BC patients-these agents only prolong survival by a few months, and patients with advanced BC remain susceptible to drug resistance. Ubiquitination, a type of post-translational protein modification, influences cellular physiological activities by regulating protein localization, stability, and activity in pathways such as gene transcription and DNA damage signaling. The reversible process of ubiquitination, termed deubiquitination, refers to the release of ubiquitinated substrates through the action of deubiquitinases (DUBs) and other active molecules. In breast cancer, an increasing number of DUBs have been identified to exhibit aberrant expression, with specific DUBs capable of either promoting or suppressing mammary tumorigenesis depending on their substrates. In this review, we focused on several DUBs associated with breast cancer, including their structure, function, and relationship to BC. Among them, we focused on the USP family and OTU family, which are more extensively studied in BC.

ACSL3 converts long-chain fatty acids into acyl-CoA, a key step in lipid metabolism. Since this process is linked to cancer development and progression, this study investigates the specific roles and underlying mechanisms of ACSL3 across various cancer types. We examined ACSL3 by analyzing its expression, transcriptomic variations, single-cell localization, prognostic significance, and biological roles using various databases and perspectives. We also studied its relationship with the immune microenvironment, epigenetic changes, and drug responsiveness. The effects of ACSL3 on liver cancer were investigated through experiments conducted both in vivo and in vitro experiments. ACSL3 was found to be abnormally expressed in most cancers, with a higher expression ratio in macrophages, and is associated with the prognosis of certain cancers, such as kidney cancer, esophageal cancer, head and neck cancer, liver cancer, lung cancer, thyroid cancer, and ovarian/cervical cancer. Its expression is closely linked to immune cell infiltration, the anti-cancer immune cycle, major histocompatibility complex, immune checkpoints, tumor mutation burden, microsatellite instability, RNA modifications like m1A, m5C, and m6A, as well as DNA methylation. ACSL3 is commonly involved in pathways related to the tumor microenvironment and cell cycle across various cancers. Experiments both in vitro and in vivo showed that reducing ACSL3 levels significantly decreased liver cancer cell growth, indicating its potential as a therapeutic target. Our research underscores the promise of ACSL3 expression as a new biomarker for forecasting the outcomes of various human cancers and assessing the effectiveness of immunotherapy.

Despite significant advances in cancer research, the complexity of signaling pathways remains a major challenge in precision oncology. Tumors harbor a diverse array of genetic alterations; however, these often converge onto a limited set of core signaling pathways, notably RAS/RAF/MEK/ERK (MAPK), PI3K/AKT/mTOR (PAM), and Wnt/β-catenin. Concurrently, these pathways diverge extensively downstream, driving therapeutic resistance through mechanisms such as epithelial-mesenchymal transition, immune evasion, and metabolic reprogramming. Unlike previous literature that largely provides descriptive accounts of pathway alterations, this review uniquely synthesizes convergent and divergent signaling into a clinically actionable diagnostic and therapeutic framework. It critically assesses current precision oncology strategies, identifies gaps, and proposes a dual-axis model that integrates static genomic profiling with dynamic signaling evolution to inform precision therapy. By highlighting opportunities for combination therapy informed by pathway interdependencies and adaptive resistance mechanisms, this perspective provides novel clinical insights and tangible directions for future research in overcoming resistance in cancer treatment.

In this preclinical human immune system patient-derived xenograft (HIS-PDX) model and phase II clinical trial, we assessed evorpacept (anti-CD47 engineered fusion protein with inactive Fc), cetuximab, and pembrolizumab (triple therapy) in microsatellite-stable (MSS) colorectal cancer.

The aim of this study is to demonstrate the real-life efficacy of BRAF and MEK inhibitors in patients with advanced thyroid cancer.

We describe a case of a young girl diagnosed with vascular malformation of the left ovary and genetically confirmed Cowden syndrome.

CD44 serves a dual role in supporting tumor survival and promoting invasion. Claudin‑low breast cancer, characterized by a CD44+/CD24‑ phenotype and epithelial‑mesenchymal transition (EMT), displays aggressive behavior. The present study investigated the interaction between CD44 and TGF‑β signaling, and assessed the cellular effects of their combined inhibition. CD44 was knocked down in claudin‑low breast cancer cell lines (SUM159 and MDA‑MB‑231), and the TGF‑β receptor (TGFBR) inhibitor LY2109761 (LY‑61) was applied for treatment. Cell viability (MTT assay), apoptosis (annexin V assay), invasion (Transwell assay), colony formation and Smad2 phosphorylation (western blotting) were evaluated. CD44 knockdown reduced viability and increased apoptosis but did not markedly suppress invasion. Although TGF‑β stimulation enhanced Smad2 phosphorylation, CD44 knockdown alone did not increase Smad2 activation, indicating that it does not directly regulate Smad2. However, LY‑61 inhibited TGF‑β‑induced Smad2 phosphorylation, effectively counteracting pro‑invasive signaling. Notably, while CD44 knockdown alone had a negligible impact on invasion, its combination with LY‑61 markedly reduced the invasive capacity and colony formation of cells compared with the control (control cells transduced with non‑targeting short hairpin RNA without LY‑61 treatment). LY‑61 induced S phase accumulation, which was more pronounced in SUM159 cells than in MDA‑MB‑231 cells, indicating cell line‑specific effects on cell‑cycle regulation. Clinical data indicated that low CD44 expression was associated with improved survival in patients with claudin‑low breast cancer, despite its potential to enhance EMT signaling. These findings suggested that CD44 knockdown enhanced the response to TGFBR inhibition. Although CD44 depletion may increase EMT‑related signaling, invasion was primarily suppressed by TGF‑β blockade, and the combination with CD44 knockdown further enhanced the inhibition of proliferative phenotypes compared with either treatment alone. This dual‑targeting approach warrants further investigation in claudin‑low breast cancer.

Esophageal cancer (EC), a malignant tumor occurring in the upper gastrointestinal tract, is the seventh most common cancer worldwide. Zinc finger proteins (ZNFs), the most abundant family of transcription factors in humans, serve an important role in the initiation and progression of various malignant tumors. However, the function of ZNFs in EC remains unclear. The present study aimed to elucidate the role of ZNF514 in the development and progression of EC and to investigate its underlying mechanism. The mRNA and protein expression levels of ZNF514 were assessed using reverse transcription‑quantitative PCR and western blotting. To assess functional roles, multiple cellular assays were performed, including 5‑ethynyl‑2'‑deoxyuridine incorporation, Cell Counting Kit‑8, wound healing, colony formation and Transwell assays. Subsequently, for transcriptomics analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis (IPA) were performed. In EC, ZNF514 exhibited high expression at both the mRNA and protein levels. Additionally, ZNF514 influenced the migration, invasion and proliferation of EC cells. Gene enrichment analyses and IPA demonstrated that ZNF514 knockdown significantly affected multiple signaling pathways, such as Fcγ receptors, the complement system, G‑protein coupled receptors (GPCRs)‑related receptors, the ribosomal S6 kinase (RSK) pathway, Ras/MEK, PI3K/AKT, STAT3, nucleotide‑binding oligomerization domain‑containing protein (NOD) and NF‑κB pathways. In conclusion, the present study indicated that the anticancer mechanisms induced by ZNF514 knockdown may be related to the enhancement of Fcγ receptor and complement system activation, as well as the inhibition of GPCR, RSK, Ras/MEK, PI3K/AKT, STAT3, NOD1/2 and NF‑κB pathways.

Following the publication of the above paper, it was drawn to the Editor's attention by an interested reader that, regarding the western blot data shown in Fig. 5 on p. 507, the first set of GAPDH bands for the GH3 cell line were strikingly similar to the EGFR protein bands shown for the GT1‑1 cell line in the adjacent set of gels, such that the same data had apparently been used to represent the two different proteins. The authors were contacted by the Editorial Office to offer an explanation for the apparent duplication of data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 47: 500‑510, 2011; DOI: 10.3892/ijmm.2020.4807].

Ubiquitination is a highly conserved and indispensable post‑translational modification in eukaryotic systems, serving as a fundamental regulatory mechanism for protein homeostasis and function. The RING finger protein (RNF) family, distinguished by their characteristic RING domains, constitute a major class of E3 ubiquitin ligases that orchestrate substrate specificity and ubiquitin transfer, thereby modulating diverse cellular processes. Accumulating evidence over the past decade has firmly established the pivotal involvement of RNF proteins in various pathological conditions, including infectious diseases, autoimmune disorders and malignancies. The present review systematically examined the mechanistic contributions of RNF family members to leukemogenesis, with particular emphasis on their regulatory roles in disease progression and therapeutic resistance. By synthesizing current knowledge, it highlighted the emerging potential of RNF proteins as both prognostic biomarkers and therapeutic targets in leukemia and advocate for the development of selective RNF‑targeting inhibitors as a promising strategy for leukemia treatment.

To understand how genetic (homologous recombination repair [HRR], including BReast CAncer [BRCA]) testing is being embedded in clinical practice and identify testing challenges given global approvals of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPis) for metastatic prostate cancer (mPCa).

Renal cell carcinoma (RCC) histological subtypes clear cell RCC (ccRCC; >75% of cases) and papillary RCC (papRCC; ∼15%) exhibit distinct molecular and genetic profiles, patient demographics, and prognoses. Previous epidemiologic studies have identified several risk factors for overall RCC, although few have explored differences in etiology across subtypes.

Burkitt's lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma, known for its rapid tumor growth and poor prognosis. Transforming growth factor beta-inhibited membrane-associated protein (TIMAP) is a regulatory subunit of protein phosphatase 1 catalytic subunit, enriched in lymphoid tissues, and upregulated in various cancers. Despite suggestions that TIMAP promotes lymphomagenesis in a c-myc-driven model, its precise role remains unclear. This study aimed to investigate the contribution of TIMAP to B-cell lymphomagenesis by examining transcriptomic changes upon TIMAP downregulation in BL cells. Raji BL cells were transfected with 2'Fluoro Arabinonucleic acid (FANA)-antisense oligonucleotides (ASO) targeting TIMAP (FANA-ASO-TIMAP) or a scramble control (FANA-ASO-Scramble). TIMAP expression was significantly reduced at the mRNA (0.70 ± 0.04, p = 0.001) and protein levels (median = 0.73, IQR = 0.13, p = 0.002). RNA sequencing identified 2,368 differentially expressed genes (DEGs), of which 1,326 were upregulated, and 1,042 were downregulated. Gene Ontology analysis revealed that the DEGs were primarily involved in cellular processes, DNA replication, intracellular signal transduction, and apoptosis. Pathways related to lymphoma progression, such as B-cell receptor signaling, p53 signaling, and mTOR signaling, were notably affected. Key genes such as PAK3, LINC00487, AID, PURPL, and BCL2 were among the most dysregulated, highlighting TIMAP's role in critical oncogenic pathways in B-cell Lymphoma. These findings suggest that TIMAP is a key regulator of gene expression and signaling pathways in B-cell lymphomagenesis and could serve as a potential therapeutic target for novel treatments.

Gene therapy has emerged as a transformative therapeutic strategy for addressing genetic disorders, refractory cancers, and infectious diseases; however, its clinical translation is significantly hindered by the lack of efficient, safe, and targeted gene delivery vectors. Conventional viral vectors are limited by immune rejection, narrow packaging capacity, and potential biosafety risks, while early nonviral vectors often suffer from poor targeting ability, low intracellular delivery efficiency, and insufficient protection of genetic cargo. Thus, the development of advanced gene delivery vectors is critical to overcoming these bottlenecks, safeguarding the stability and bioavailability of genetic materials, and unlocking the full therapeutic potential of gene-based therapies. Metal-organic frameworks (MOFs) are a new type of porous nanomaterial with substantial potential for use in gene delivery due to their large specific surface area, tunable pore size, good biocompatibility, and low toxicity. Here, we present a comprehensive review of MOF synthesis strategies, gene delivery mechanisms, and associated progress in biomedical applications. Genes can be effectively loaded onto MOFs through pore encapsulation, surface adsorption, covalent binding, and in situ encapsulation. Subsequently, surface functionalization methods are used to achieve precise delivery. In tumor-targeted therapy, MOFs can specifically recognize cancer cells and release genes in response to the microenvironment, thereby significantly inhibiting tumor growth. In the field of immune regulation, MOF multifunctionality supports the codelivery of genes and immune drugs, synergistically enhancing the antitumor immune response. However, challenges remain in the clinical application of MOFs, including insufficient biostability, low intracellular delivery efficiency, and potential toxicity. These challenges are expected to be addressed in the future through the development of new stable MOF materials, the optimization of surface engineering strategies, and the construction of intelligent responsive systems, yielding more precise and efficient gene therapy development.

Lung adenocarcinoma (LUAD) is one of the common malignant tumors worldwide, and the 5-year survival rate remains unsatisfactory. To investigate the association between disulfidptosis-related ferroptosis genes (DFRGs) and the prognosis of patients with LUAD, establish a risk prognostic model, validate key biomarkers in vitro, and provide references for the prognosis of LUAD patients.

To investigate the expression and clinical significance of CXCR7 and TAGLN2 in papillary thyroid carcinoma (PTC), and to explore the molecular mechanisms underlying the interaction between CXCR7 and TAGLN2 in regulating PTC invasion and metastasis.

Hepatocellular carcinoma (HCC) faces challenges in early diagnosis, prognosis, and treatment stratification due to molecular heterogeneity. This study aimed to establish a plasma exosomal long non-coding RNA (lncRNA)-based framework for molecular classification, prognostication, and therapeutic guidance in HCC.