Hepatocellular carcinoma (HCC) represents a critical oncological challenge demanding innovative therapeutic interventions. miRNA has been known to play an important role in cancer inhibition to control HCC's development and progression by regulating cell proliferation and apoptosis. The major hurdle is to deliver the miRNA at the site of tumor. Metallic nanoparticles with modified surface can be used to solve this problem. In the current study, gold-nanoparticles (Au NPs) were prepared, and their surface was modified with PEG moiety to facilitate the attachment of miRNA. For the first time, the modified gold NPs were loaded with miR-199a. Our findings revealed that, when cells treated with gold bare (80 nM) for 24 h, a low cytotoxicity was obtained (11.11 ± 2.25%). When cells treated with nanocomplex miRNA- PEG -Au NPs (80 nM) for 24 h, a significantly increased cellular cytotoxicity was obtained (55.7 ± 4.55%). Also, the prepared nanocomplex exhibits a promising potential in suppressing tumor cell proliferation and significantly enhancing apoptosis in a concentration and time dependent manner. These results underscore the transformative potential of targeted nanomaterial-based miRNA delivery as a sophisticated therapeutic modality in cancer management. In conclusion, Au NPs are excellent carriers for miRNA where they increase the cellular uptake, exerting a promising anticancer effect on HCC cells, representing a new approach in developing precision therapeutics for hepatocellular carcinoma.

Osteosarcoma is a highly malignant bone tumor which primarily affects the juvenile population and is characterized by high rate of recurrence and metastasis. RNA editing has emerged as a key process in cancer progression. Herein, we investigated the role of RNA editing enzyme ADAR2 (Adenosine Deaminase Acting on RNA 2) in osteosarcoma. We demonstrated that ADAR2 expression increases during osteoblast differentiation and inversely correlates with the aggressiveness of osteosarcoma cells. Interestingly, the overexpression of ADAR2 in osteosarcoma cell lines reduces their tumoral properties and promotes their differentiation in osteoblast-like cells, as shown by gene expression analysis and mineralization assays. These results were also confirmed by in vivo experiments; indeed, intratibial injection of ADAR2-overexpressing osteosarcoma cells in NSG mice resulted in less aggressive tumors compared to mice injected with pEmpty or pInactive ADAR2 E/A vector-transfected cells. To elucidate the mechanisms by which ADAR2 overexpression induces osteogenic terminal differentiation of osteosarcoma cells, we performed RNA-seq analysis of Saos-2 cells and identified IGFBP7 (Insulin-like Growth Factor Binding Protein 7) as the most highly edited transcript in ADAR2-overexpressing cells. We showed that the editing activity of ADAR2 on IGFBP7 abolishes its proliferative effect on osteosarcoma cells and triggers terminal differentiation. Overall, our results indicate that ADAR2 acts as a tumor suppressor in osteosarcoma and may represent a novel therapeutic target for this aggressive pediatric tumor.

The RHO GTPase family regulates cytoskeleton-dependent processes, including proliferation and migration. Although their dysregulation is well described in solid tumors, little is known about their role in hematologic malignancies. We investigated the expression of ten RHO GTPase genes in bone marrow samples from patients with acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) and analyzed TCGA AML data for prognostic associations. RHOBTB2, RND2, and RHOQ were differentially expressed compared with healthy controls. RHOBTB2 was elevated in both MDS and AML and associated with inferior overall and disease-free survival, including in intermediate-risk AML. Our findings reveal distinct dysregulation patterns of RHO GTPases in myeloid malignancies and confirm RHOBTB2 as a candidate prognostic marker in AML with a potential oncogenic role. These data support further investigation into the functional roles of RHO GTPases in leukemogenesis and their utility as emerging biomarkers in hematologic cancers.

Extrachromosomal circular DNA (eccDNA) are molecules that originate from chromosomal DNA but exist independently. While large eccDNA (ecDNA) contributes to tumorigenesis, the role of smaller eccDNA (<100,000 base pairs) in cancer remains unclear. Our analysis of 25 colorectal cancer (CRC) tumors and normal adjacent tissues revealed that eccDNA is significantly more abundant in tumor tissues, correlating strongly with chromosomal amplifications. The presence of whole intact genes on 1.29% of eccDNA was nonrandom. We identified 84 genes that recurred across tumors of multiple patients when present on eccDNA, with 19% of genes being cancer-associated. eccDNA-borne genes were often accompanied by increased expression, and their contribution to expression was much larger than that from linear amplifications and the larger ecDNA. The cytokine gene CXCL5 exemplified this phenomenon, showing substantial copy-number increase and upregulation when present on eccDNA. Functional validation in cell lines showed that CXCL5 eccDNA enhanced transcriptional output and immune cell recruitment function. The recurrence and overexpression of CRC-related genes on eccDNA indicate their selection in tumors, suggest that eccDNA can serve as an additional mechanism for dynamically influencing gene expression and is capable of conferring cancer phenotypes on cells. Analysis of chromatin landscapes revealed that eccDNA preferentially forms at sites of open chromatin and active transcription, with architectural boundaries marked by CTCF protein. Clinically, higher eccDNA levels correlated with poorer relapse-free survival in a small patient cohort. These findings suggest that circular DNA elements across the entire size spectrum participate in cancer evolution and warrant further investigation in larger cohorts.

Non-small cell lung cancer (NSCLC) is a malignant tumor characterized by high morbidity and mortality, as well as metabolic reprogramming. Enhanced serine synthesis plays a crucial role in the aberrant metabolism of NSCLC. Among the three key enzymes involved in serine synthesis, phosphoserine aminotransferase 1 (PSAT1) requires further investigation to elucidate its regulatory mechanisms in NSCLC.

Thrombocytopenia-absent radius (TAR) syndrome is a rare congenital disorder characterized by bilateral radial aplasia with preserved thumbs and early-onset thrombocytopenia. While hematologic and skeletal abnormalities define the condition, its association with hematologic malignancies is extremely rare, with only a few reported cases of leukemia. Juvenile myelomonocytic leukemia (JMML) is an uncommon pediatric myelodysplastic/myeloproliferative neoplasm frequently linked to RAS pathway mutations. To our knowledge, JMML has not previously been reported in association with TAR syndrome.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid malignancies, characterized by aggressive biology and a paucity of effective treatments. Activating mutations in KRAS occur in more than 90% of cases and are fundamental to tumor initiation, progression, therapeutic resistance, and immune exclusion, establishing KRAS as the dominant oncogenic driver in PDAC. Long considered undruggable, KRAS has recently become a viable therapeutic target with the development of allele-specific inhibitors as well as pan-RAS(ON) agents capable of broadly suppressing mutant RAS signaling. Preclinical models and early-phase clinical trials demonstrate meaningful antitumor activity, with emerging evidence of tumor microenvironment remodeling and delayed resistance. Combination strategies integrating KRAS-directed therapies with chemotherapy, vertical pathway inhibition, immunotherapy, and emerging approaches such as KRAS degradation and RNA-targeted approaches are being explored to improve the depth and durability of response. Together, these advances signal a paradigm shift toward molecularly guided treatment strategies in PDAC and offer a promising path forward in a disease with substantial unmet clinical need.

Hsa-miR-99a has been linked to the advancement of several malignancies, including colorectal cancer (CRC). This investigation seeks to elucidate its function and regulatory network in CRC.

Gastric carcinoma poses a significant global health challenge, often diagnosed late due to its similarity to chronic gastric conditions. Helicobacter pylori (Hp) infection plays a crucial role in gastric carcinogenesis through inflammation and the release of virulent products.

T cell dysfunction (TCD) plays a critical role in cancer progression and significantly impacts patient outcomes. Despite its importance, the exact molecular mechanisms underlying TCD remain poorly understood. To address this, we constructed a comprehensive pan-cancer landscape of TCD, with a particular focus on identifying miRNA biomarkers that define and predict TCD severity. Our analysis revealed six key miRNAs (miR-203b, miR-214, miR-4772, miR-141, miR-200a, and miR-200b) that were closely associated with varying degrees of TCD. These prognostic miRNAs not only exhibited distinct expression patterns across four identified TCD subtypes (from low to high TCD severity) but also demonstrated strong predictive performance in classifying patients with different levels of TCD. The identified miRNA signatures serve as reliable biomarkers for stratifying patients into high-risk and low-risk groups, with higher TCD levels correlating to poorer overall survival. In addition to miRNA biomarkers, we observed that patients with severe TCD exhibited increased infiltration of immune cells and macrophages and dysregulation of DNA methylation patterns. Patients with higher degrees of TCD displayed low methylation levels, which further contributed to the progression of T cell dysfunction. In summary, our study highlights the pivotal role of miRNA biomarkers in shaping the landscape of T cell dysfunction across cancers. These miRNAs serve as both prognostic indicators and predictive tools, enabling accurate classification of TCD severity and offering new avenues for therapeutic exploration and patient stratification in cancer immunotherapy.

Tensins are a family of adhesion proteins that play a role in constructing the cytoskeleton, as well as in intracellular and extracellular communication. Their expression was evaluated in 22 pancreatic cancer patients using the immunohistochemistry method. TNS1 expression occurred more frequently among patients with tumor diameter ≥ 2 cm, which may suggest an association with the development of pancreatic cancer. Intraductal TNS1 was observed less often with presence of necrosis and hemorrhages in tumor. The fact that cancer cells secrete TNS1 suggests that it could be investigated as a potential target for liquid biopsies. TNS4 expression occurred more frequently among females and was observed when necrosis in tumor was strong. TNS2 and TNS3 are not involved in the development of ductal pancreatic adenocarcinoma.

T helper 17 cells play essential roles in mucosal immunity and autoimmunity, yet the mechanisms that protect these cells from oxidative DNA damage remain poorly defined. Here we show, in a murine model, that the nucleotide excision repair sensor Xeroderma Pigmentosum Complementation Group C preserves genomic stability and metabolic fitness during T helper 17 cell differentiation. Loss of this factor reduces interleukin 17 production and increases mitochondrial reactive oxygen species and oxidative DNA damage, resulting in altered metabolic programs. Mechanistically, Xeroderma Pigmentosum Complementation Group C interacts with the base excision repair enzyme 8-oxoguanine DNA glycosylase, and its absence enhances oxidative lesion incision activity, indicating defective coordination between DNA repair pathways. Restoring antioxidant capacity rescues cytokine production and limits DNA damage in deficient cells. Together, these findings identify Xeroderma Pigmentosum Complementation Group C as a key coordinator of DNA repair and redox control required for T helper 17 cell function in inflammatory settings.

Approximately 70% of clear cell renal cell carcinoma (ccRCC) patients harbor von Hippel‒Lindau (VHL) deficiency, which drives pseudohypoxia and metabolic reprogramming. Here, we report a histone H4 lysine 12 lactylation (H4K12la)-fueled phosphoglycerate kinase 1 (PGK1)-lactate positive feedback loop that sustains glycolytic flux in VHL-deficient ccRCC and is pharmacologically disruptable by glucocorticoids. H4K12la is markedly elevated in ccRCC tissues and is associated with advanced pathological stage and unfavorable patient outcome. Integrative transcriptomic and epigenomic profiling revealed that VHL deficiency amplifies H4K12la deposition at accessible promoters, coupled to transcriptional activation of glycolytic and tumor-promoting programs, exemplified by PGK1. Through high-content drug screening, we identify glucocorticoids as effective suppressors of H4K12la, which act via glucocorticoid receptor-mediated transcriptional repression of glycolytic genes and consequent attenuation of lactate production. Strikingly, VHL-deficient ccRCC exhibits greater on-target pathway sensitivity to dexamethasone at the H4K12la-glycolysis axis, and glucocorticoid dexamethasone potentiated the antitumor efficacy of the HIF-2α inhibitor belzutifan in both orthotopic cell line-derived and patient-derived xenograft models. Collectively, our findings establish H4K12la as a metabolic‒epigenetic amplifier in VHL-deficient ccRCC, reposition glucocorticoids as epigenetically active modulators that dampen lactate-driven chromatin activation and glycolytic output, and provide a mechanistically grounded combination strategy with HIF-2α blockade to target lactate-fueled transcriptional dependence in metabolically rigid tumors.

To clarify the karyotype evolution of multiple myeloma (MM), multiple karyotypes of 22 patients with MM were analyzed using G-banding, and their karyotype evolutions were depicted as phylogenetic trees. Eleven patients exhibited highly complex karyotype evolutions, combining branched evolution, linear evolution, parallel evolution and macroevolution. While chromosomal structural abnormalities involving 14q32 were detected at the roots of the phylogenetic trees of karyotype evolution, aneuploidies and the other structural abnormalities were identified in both the initial clones and karyotypically evolved subclones. The findings indicated that aneuploidies might be caused by unequal chromosomal segregation, loss of the chromosome with unbalanced whole-arm translocation, and whole-chromosome doubling in patients with near-tetraploidy. Four patients had karyotype abnormalities (three del(20)(q) and one del(5)(q)) associated with myelodysplastic syndrome independent of the karyotype evolution of MM. In conclusion, the phylogenetic trees depicted by G-banding present the karyotype evolution of MM.

Insufficient T-cell infiltration limits the effectiveness of immunotherapy in sarcoma, yet the tumor-intrinsic mechanisms that govern immune exclusion remain poorly defined.

Cancer-associated fibroblasts (CAFs) represent a predominant cell population in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). How the spatial distribution of CAF subtypes relates to immune modulation within the TME remains incompletely understood. This study aimed to characterize the spatial organization of CAF subtypes in HCC and to explore their potential associations with immune contexture.

Mucosal melanoma (MM), an aggressive melanoma subtype arising in mucosal tissues, displays resistance to therapies effective in cutaneous melanoma. To understand how mucosal microenvironment contributes to treatment nonresponsiveness, we performed integrative analysis of single-cell and bulk messenger RNA sequencing data derived from oral mucosa-originated melanoma and revealed that mucosa-specific inflammation induces enrichment of low-pigmented neural crest-like cancer cell, mediated by COX2+ macrophages and their secretome. Maintenance of this inflammation-induced neural crest-like state in cancer cells depends on HER2 and HER3 activation. Inhibition of HER2/3 by pan-HER inhibitors blocks cell state plasticity and overcomes chemoresistance in primary MM cell lines and patient-derived xenograft (PDX) models. These findings provide insights into how the tissue of origin determines cancer aggressiveness, highlight the role of mucosal inflammation in driving melanoma stemness and chemoresistance, and advance the identification of effective treatment options currently lacking for patients with MM.

Targeted therapies have significantly transformed the management of chronic lymphocytic leukaemia (CLL), yet most recommendations continue to reflect Western practice patterns. Variations in disease biology, healthcare resources and treatment accessibility across the Asia-Pacific (APAC) necessitate region-specific guidance. The Asia-Pacific Leukaemia Consortium (APLC) therefore developed updated consensus statements to support standardised, context-appropriate care for patients with CLL.

Despite the remarkable success of immune checkpoint inhibitor (ICI) therapy in solid tumors, immune-related adverse events (irAEs) have posed great challenges in the whole-course management of ICI immunotherapy. Reliable biomarkers helping to predict irAEs are still limited and lacking.

The prognostic value of TP53 mutations in metastatic colorectal cancer remains unclear owing to inconsistent findings in the literature. Given its central role in tumor biology, clarifying the impact of TP53 status on survival outcomes is clinically relevant.