Therapeutic resistance is a major obstacle in cancer treatment, often leading to recurrence and death. SUMOylation is a dynamic and reversible process of post-translational modification through a strict enzyme cascade that regulates the modification of target proteins by SUMO1-5 and SENP family proteins, which are involved in regulating protein stability, function, and localization to influence biological pathways, including cancers. SUMOylation contributes significantly to cancer drug resistance, undermining the efficacy of clinical treatment. Therefore, studying the role of SUMOylation in the development of cancer drug resistance has significant prospects. This review focuses on the important mechanistic role of SUMOylation in promoting or inhibiting cancer drug resistance and summarizes the feasibility of using SUMOylation as a therapeutic target for cancer treatment by combining SUMOylation inhibitors and anticancer drugs, which will provide new insights into overcoming cancer drug resistance and clinical cancer treatment.

Natural polysaccharides are increasingly recognized for their immunomodulatory and antitumor properties. This study evaluated the effects of Lemon Gum (LG), a polysaccharide from Citrus × latifolia, on in vitro cytotoxicity and in vivo antitumor activity in BALB/c mice bearing murine colon tumors. Cytotoxicity was assessed using the MTT assay in CT26.WT, B16-F10, and L929 cell lines. In the animal model, tumor inhibition following treatment, relative organ weight, as well as biochemical, hematological, and histopathological parameters were evaluated to determine the systemic effects of the treatment, in addition to the expression of inflammatory cytokines analyzed by qRT-PCR. LG showed no cytotoxicity in vitro but exhibited antitumor effects in vivo, with tumor inhibition rates of 16.46% and 33.16% at 50 and 100 mg/kg/day, respectively. No significant biochemical or hematological toxicity was detected, although a slight increase in relative liver weight occurred at both doses. Histopathology revealed mild, potentially reversible hepatic alterations. qRT-PCR analysis demonstrated upregulation of Il1b, Ifng, Tlr4, and Il12 with no significant changes in Il4, Il6, Il18, Il33 and Tgfb expression across the experimental groups. These findings indicate that LG exerts moderate in vivo antitumor activity, potentially linked to immunostimulatory mechanisms, and displays a favorable safety profile, supporting its potential for further biomedical investigation.

Levan, a fructose-based polysaccharide, has been widely reported to exhibit broad-spectrum antibacterial activity, highlighting its potential for biomedical applications. While its antimicrobial efficacy has been demonstrated, the global bacterial transcriptional responses associated with levan exposure remain insufficiently characterized. In this study, we investigated the cellular and transcriptional responses of Escherichia coli to levan treatment using differential gene expression (DGE) analysis and transmission electron microscopy (TEM). TEM observations suggested that levan exposure is associated with osmotic stress, as evidenced by cell shrinkage, leakage of intracellular components, and growth inhibition. Transcriptomic analysis indicated alterations in multiple pathways, including a shift toward anaerobic metabolism, activation of fermentation-related processes that may contribute to acidic stress, and reduced expression of genes involved in cysteine and sulfate uptake. Additionally, levan treatment was associated with decreased expression of genes linked to chromosome segregation, cell division, biofilm formation, adhesion, quorum sensing, and motility. Collectively, these findings provide putative transcriptomic insights into how levan may influence bacterial physiology and offer a foundation for future mechanistic and validation studies.

Cypermethrin, a type II pyrethroid insecticide, is widely used worldwide, but its potential teratogenicity remains a cause for concern. The present study aimed to investigate the dose-dependent effects of cypermethrin on neural tube development in early-stage chick embryos. Specific pathogen-free fertilized eggs (n = 125) were divided into five groups and treated subblastodermally at the 28th hour of incubation with saline (control) or cypermethrin at 0.01, 0.1, 1, or 10 ppm. The embryos were dissected after 48 h and evaluated for morphological, immunohistochemical, and genetic findings. Morphological analysis revealed a significant increase in open neural tube frequency, reduced crown-rump length, and decreased somite number at 1 and 10 ppm (p < 0.05). Immunohistochemical findings showed a dose-dependent increase in Caspase 3 and TUNEL indices, accompanied by a significant reduction in PCNA at higher concentrations (p < 0.001). Gene expression analysis revealed a consistent downregulation of transcription factor AP-2 (TFAP2) at all doses (p < 0.001), a non-significant alteration in brain and reproductive organ-expressed protein (BRE) (p > 0.05), and a significant upregulation of T-box transcription factor 18 (TBX18) at 10 ppm (p < 0.001). In conclusion, cypermethrin exposure during post-gastrulation impairs neural tube closure in chick embryos through enhanced apoptosis, reduced proliferation, and transcriptional dysregulation. These findings provide experimental evidence of the embryotoxic potential of pyrethroids and emphasize the need for stricter regulation of pesticide use to minimize developmental risks.

With unprecedented climate change, coastal overtopping is projected to increase up to 50-fold by 2100. Unlike complete flooding, overtopping imposes a salt-submergence stress for plants by combining oxygen (O2) deficiency with elemental toxicity. To address this, we investigated whether S-nitrosoglutathione (GSNO), a stable nitric oxide (NO) donor, could mitigate these dual stresses-submergence (Sub) and salt-mixed Sub (Salt + Sub)-in two Korean japonica rice varieties, Ilmi and Samgwang. Under Sub stress, both varieties relied on internode elongation and aerenchyma formation as escape strategies; however, these responses were significantly impaired under Salt + Sub. GSNO pretreatment effectively counteracted this impairment, not only by restoring the growth defects, but also improving overall biomass under both stresses. This response was mediated by ethylene, gibberellic acid (GA), and abscisic acid (ABA). Specifically, GSNO pretreatment reduced the level of ABA but increased the intermediates of GA and the relative expression of ethylene-related genes, ACO5 and EIN3, under both stress conditions. These changes led to downstream expression of marker genes associated with cell wall expansion, energy conservation, and ethylene signaling, particularly in Samgwang under Salt + Sub conditions. GSNO-treated Samgwang plants consistently outperformed Ilmi in terms of survival, largely due to improved detoxification of reactive oxygen species (ROS). Additionally, GSNO upregulated expression of Na+ transporter genes (SOS1, SOS2, HKT1, and NHX1), indicating improved Na+ extrusion and sequestration, thereby maintaining ion homeostasis during combined stress. Overall, GSNO conferred multifaceted protection against Sub and Salt + Sub stresses by improving hormonal balance, ROS-detoxification, and ion transport. These findings highlight GSNO's potential in conferring rice resilience to climate change-driven coastal challenges.

Breast cancer progression is driven by aberrant signaling pathways that include proliferation, apoptosis, and cytoskeletal remodeling. While tamoxifen remains central to breast cancer therapy, its clinical utility is restricted by developing resistance and toxicity, prompting the need for safer alternatives. To this end, glycyrrhizin, a triterpenoid saponin derived from Glycyrrhiza glabra, has shown activity against different cancers, yet its exact role in breast carcinogenesis remains elusive. In the present study, the effects of glycyrrhizin and tamoxifen were evaluated in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma model. Both treatments significantly delayed tumor onset, reduced incidence, and decreased overall tumor burden. Histopathology revealed that DMBA exposure produced predominantly high-grade adenocarcinomas, whereas preventive glycyrrhizin and tamoxifen markedly reduced tumor grade to well-differentiated lesions. Curative protocols using glycyrrhizin and tamoxifen eliminated high-grade features. Gene expression studies indicated downregulation of oncogenic drivers (c-Myc, stathmin, cyclin D1, RAN, α-tubulin) and suppression of the anti-apoptotic protein Bcl-2. Both agents increased p53 mRNA expression, modulated interferon-γ expression, and decreased HSP84 expression. Importantly, glycyrrhizin uniquely enhanced PTEN mRNA expression versus tamoxifen, suggesting a potential influence on PI3K/AKT-related signaling. Protein expression analysis of cyclin D1 and α-tubulin demonstrated reduced levels, consistent with disrupted cell-cycle progression along with compromised cytoskeletal integrity. Collectively, these findings indicate that glycyrrhizin exerts anticancer activity associated with modulation of multiple cancer-related genes and histopathological regression, with a distinctive impact on PTEN mRNA expression and cytoskeletal regulators. These data support glycyrrhizin as a promising natural compound for breast cancer and warrant further protein-level mechanistic and translational evaluation.

Lipid metabolism disorders and increased angiogenesis play key roles in the tumorigenesis of hepatocellular carcinoma (HCC). Intracellular metal ion disorders such as cuproptosis and ferroptosis have been progressively identified. However, whether copper ions have other effects outside the already recognized mechanisms of cell death is just as worthy of investigation. In particular, the effects on lipid metabolism and angiogenesis have important roles in the development of HCC. Our study revealed that disulfiram (DSF), a copper ion carrier, not only had a significant antitumor effect in vitro and in vivo, but also significantly inhibited angiogenesis and reversed abnormal lipid metabolism. Through transcriptome analysis, m1A methylation analysis, and functional validation, we identified c-FOS as a key target in DSF-induced methylation changes. In summary, DSF can reduce the modifications of c-FOS caused by the m1A methyltransferase TRMT10C, then regulate downstream genes MCAM and PCSK9, ultimately affecting angiogenesis and lipid metabolism. Moreover, high levels of expression of TRMT10C and PCSK9 in human HCC tumor tissues were associated with poor prognosis, while c-FOS showed the opposite pattern, confirming that the TRMT10C-c-FOS-PCSK9 axis is an important mechanism in HCC. In conclusion, copper ion carrier-DSF promotes the expression of c-FOS by inhibiting the m1A methyltransferase TRMT10C, thereby reversing the dysregulation of lipid metabolism and inhibiting angiogenesis in HCC.

Phosphorus deficiency is a critical abiotic stress that limits crop productivity, severely constraining plant photosynthesis by inhibiting light reactions and carbon assimilation. Methyl jasmonate (MeJA), as a key stress signaling molecule, plays a central regulatory role in plant adaptation to low-phosphorus environments. This article systematically reviews the physiological and molecular mechanisms by which exogenous MeJA alleviates photosynthetic inhibition under low-phosphorus stress, with a focus on its integration of phosphorus starvation and jasmonate signaling pathways through the PHR1 (PHOSPHATE STARVATION RESPONSE 1)-JAZ-MYC2 signaling module. This, in turn, coordinates a multi-layered network involving the regulation of photosynthetic enzyme activity, antioxidant defense, and phosphorus uptake and recycling. The article also explores potential approaches for improving crop phosphorus efficiency through the jasmonate signaling pathway. This review aims to provide a theoretical foundation for understanding plant phosphorus-hormone interaction mechanisms and offer new insights for stress resistance regulation and genetic improvement in crops.

Neisseria gonorrhoeae (Gc) is the gram-negative bacterium that causes gonorrhea, a prevalent sexually transmitted infection that can have life-threatening clinical sequelae. Gc requires iron for human infection and uses the iron-responsive, iron-binding transcriptional repressor Fur to maintain iron homeostasis. Gc infects mucosal sites, where the neuroendocrine hormone norepinephrine (NE) is produced by the autonomic nervous system and various epithelial and immune cell types. Here, we show that NE derepresses the Fur regulon to alter bacterial iron homeostasis and increase Gc survival. By RNA-seq, we determined that NE rewires gonococcal gene expression to increase capacity for iron uptake while enabling increased intracellular iron availability. Of the 30 genes that were differentially expressed in NE-treated compared to untreated bacteria, 27 have Fur box-containing promoters. A possible mechanism for how NE derepresses the Fur regulon is through direct demetalation of Fur, as NE directly decreased binding of Fur in vitro to a DNA amplicon containing the Fur-binding sequence from Gc tbpB. NE increased the labile intracellular iron pool in Gc, evidenced by increased streptonigrin sensitivity, without significantly increasing the total bacterial iron content, suggesting that NE leads to the redistribution of cellular iron. The work presented here provides a novel mechanism for how Gc survives iron limitation within its obligate human host.IMPORTANCENeisseria gonorrhoeae (Gc) is the bacterial pathogen that causes gonorrhea, a sexually transmitted infection with an estimated global annual incidence of 87 million individuals. During infection, Gc must overcome iron limitation imposed by nutritional immunity. Here, we show that the host neuroendocrine hormone norepinephrine, which is present at the mucosal surfaces Gc infects, promotes the survival of iron-limited Gc. Our results support a novel mechanism by which norepinephrine works through the ferric uptake regulator, Fur, to enhance the capacity of Gc to take up iron and make it bioavailable. Our findings show that Gc responds to host-derived cues that enable it to resist iron limitation.

Acquired drug resistance is a major cause of poor prognosis in multiple myeloma (MM). Bortezomib (BTZ), a first-line therapeutic agent, is highly effective in MM; however, resistance remains a significant clinical challenge. Our previous work implicated Solute Carrier Family 19 Member 1 (SLC19A1) in hypoxia and immune modulation, suggesting its potential role in malignant progression. Here, we found that SLC19A1 expression was elevated in MM patients, particularly in those with acquired resistance. Overexpression of SLC19A1 enhanced the proliferation and invasiveness of human myeloma cell lines but did not confer primary BTZ resistance. Using a continuous-BTZ-exposure model, we demonstrated that SLC19A1 overexpression mediated acquired resistance via chronic activation of the stimulator of interferon genes (STING) pathway. This sustained activation triggered the unfolded protein response, dysregulated the endoplasmic reticulum-mitochondrial axis, and induced mitochondrial DNA (mtDNA) release. Treatment with the SLC19A1 inhibitor sulfasalazine or the STING inhibitor H-151 reduced mtDNA release and restored BTZ sensitivity. These findings highlight SLC19A1 and STING signaling as potential therapeutic targets for overcoming acquired drug resistance in MM.

This study investigates how brassinosteroids (BRs) enhance stress tolerance in soybean under combined salt and drought stress by examining growth, chlorophyll content, photosynthesis, and reactive oxygen species (ROS) homeostasis. Salt and drought stress significantly reduced soybean growth and photosynthetic performance, as reflected by lower SPAD chlorophyll values and decreased photosystem II (PSII) efficiency. In contrast, BR (24-epibrassinolide, EBL) significantly improved growth parameters and spectral indices, indicating a healthier pigment status and improved canopy function. EBL-treated plants also exhibited enhanced PSII performance, as indicated by increased Fv/Fm and a higher performance index (PI). Furthermore, BRs modulated ROS levels and promoted cellular homeostasis by elevating the activities of antioxidant enzymes such as APX, CAT, and POX, thereby mitigating oxidative damage. Consistently, expression of key stress-responsive genes (GmCAT, GmSOD, and GmP5CS) was strongly induced under combined salt, drought, and EBL treatment, highlighting the synergistic role of EBL in transcriptional activation under combined stress. EBL treatment increased the proline content and the activities of ProDH and P5CS, supporting proline-mediated osmoprotection, while BR-treated plants exhibited reduced malondialdehyde (MDA) accumulation and electrolyte leakage (EL), indicating lower lipid peroxidation and better membrane integrity under stress. Overall, this study demonstrates that EBL enhances soybean resilience to combined salt and drought stress by improving growth, photosynthetic efficiency, antioxidant defense, osmotic adjustment, and membrane stability.

Preeclampsia (PE) is a pregnancy-specific hypertension with signs of other organ dysfunction. Despite its unclear mechanism, current data suggest the role of neuroinflammation in blood pressure dysregulation in PE. Considering the role of toll-like receptor 4 (TLR4) in various inflammatory conditions, we hypothesized that centrally expressed TLR4 may promote PE and that its inhibition, with pyridostigmine (PYR), may attenuate this condition in rats. Changes in TLR4 expression in the paraventricular nucleus (PVN) of reduced uterine perfusion pressure (RUPP) were assessed, as well as TLR4 sensitivity. The effect of PYR, at an oral dose of 20 mg/kg/day, on TLR4 signaling in RUPP or lipopolysaccharides (LPS, 5 µg/kg)-infused pregnant rats was assessed. On gestation day 19, mean arterial pressure (MAP) was recorded under urethane anesthesia, and PVN samples were collected and subsequently processed. Placental ischemia increased MAP (p < 0.05), TLR4 expression (p < 0.05) in RUPP, and TLR4 sensitivity in RUPP + LPS rats. LPS infusion elevated MAP to a greater extent in RUPP (37.1 ± 3.5 mmHg) compared to Sham (13.2 ± 6.5 mmHg) (p < 0.01) after 1 h. Such an effect of LPS was associated with increased expression of c-Fos (p < 0.01) in the PVN. PYR significantly reduced MAP in RUPP and LPS-treated dams, as well as TLR4 signaling proteins, ROS, TNF-α, and IL-1β in the PVN. In conclusion, placental ischemia-increased MAP is associated with high TLR4 expression in the PVN and increased TLR4 sensitivity, and PYR could attenuate TLR4 signaling in the PVN, thereby reducing blood pressure.

The application of biostimulants represents a sustainable strategy to enhance crop productivity and resilience. This study investigated the efficacy of Delonix regia pollen aqueous extract as a biostimulant on coriander (Coriandrum sativum). Seeds were primed with different concentrations of the extract (0%, 0.5%, 1%, and 1.5%) for 24-48 h. The 1% extract applied for 48 h was the most effective treatment, significantly increasing shoot fresh and dry weight, shoot length, and the content of total protein, phenolics, flavonoids, and terpenes. This treatment also led to a significant upregulation of the key biosynthetic genes Chalcone synthase (CHS) and geranylgeranyl pyrophosphate synthase (GGPS) by 1.4-fold and 2.1-fold, respectively. Principal component analysis confirmed a positive correlation among shoot fresh weight, total protein, terpene content, and GGPS expression. These findings demonstrate that D. regia pollen extract is a potent biostimulant that enhances coriander growth and the production of valuable bioactive compounds through the modulation of key metabolic pathways.

With the increasing demand for sustainable agriculture, rhamnolipids (RHAs), a class of biosurfactants, have emerged as promising eco-friendly biostimulants. However, their full potential has been limited by impurities and uncertain mechanisms. This study investigated the effects of high-purity RHAs on wheat (Triticum aestivum) growth and yield through controlled laboratory experiments and multiyear field trials. In laboratory assays, optimal RHA concentrations (5-10 mg·L-1) promoted seedling growth by enhancing chlorophyll content, root-shoot development, and tillering. Transcriptomic profiling revealed that RHA treatment upregulated genes involved in gibberellic acid (GA3) and zeatin (ZT) biosynthesis, nitrogen uptake, and photosynthesis. In the field, low doses of RHA application (∼45 g·ha-1) significantly enhanced tillering capacity and promoted earlier flowering while delaying senescence. Importantly, these physiological enhancements translated into significant yield increases of 11.9 and 14.8% across 2 consecutive years. The study provides novel mechanistic insights into RHA-mediated growth promotion, highlighting RHAs as a promising, eco-friendly biostimulant for sustainable wheat production.

Hepatocellular carcinoma (HCC) has a high mortality rate, primarily driven by metastasis. The role of the histone deacetylase inhibitor (HDACi) entinostat in this process remains controversial, limiting its clinical application. This study aims to define entinostat's function and mechanism in HCC metastasis. We employed in vitro models, transcriptomic sequencing, chromatin immunoprecipitation-qPCR, and an orthotopic mouse model to assess the effects of entinostat on epithelial-mesenchymal transition (EMT), invasion, and tumor growth. Our findings demonstrate that entinostat potently prevented and reversed transforming growth factor-β (TGF-β)-induced EMT, suppressing HCC cell invasion and metastasis in vivo without significant toxicity. Transcriptomics identified alpha-2-glycoprotein 1, zinc-binding (AZGP1) as a key target. In addition, entinostat promotes histone H4 acetylation at the AZGP1 promoter, activating its transcription. AZGP1 overexpression mimicked entinostat's effects, while its knockdown largely abolished them. Clinically, high AZGP1 expression was associated with an improved prognosis. In conclusion, our work elucidates a coherent epigenetic pathway wherein entinostat activates AZGP1 to inhibit HCC metastasis. These findings nominate AZGP1 as both a critical mediator and a potential biomarker for entinostat-based therapy in advanced HCC.

This study investigates the mechanisms by which histone deacetylase (HDAC) inhibitors induce epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC), focusing on the role of Cathepsin B. Lung cancer cell lines A549 and H1975 were treated with HDAC inhibitors SAHA and SB939, and various assays were conducted to assess cell viability, apoptosis, migration, invasion, and cytoskeletal changes. The expression of EMT-related proteins and Cathepsin B was analyzed using Western blotting, immunofluorescence, and quantitative PCR. The results demonstrated that HDAC inhibitors reduced cell viability and increased apoptosis while promoting EMT phenotypes, enhancing migration and invasion. Cathepsin B was identified as a key mediator of the HDAC inhibitor-induced EMT, which it promotes by interacting with and upregulating the transcription factor Slug. These findings suggest that Cathepsin B is a crucial factor in HDAC inhibitor-induced EMT in NSCLC, indicating that targeting this enzyme may provide a novel therapeutic strategy to counteract invasiveness in lung cancer.

This study aimed to investigate antimicrobial effects of caffeic acid (CA) against multidrug-resistant Vibrio parahaemolyticus and Vibrio cholerae both in vitro and in shrimp (Penaeus vannamei). CA at concentrations of 0.47-0.94 mg/mL disrupted bacterial membrane integrity, resulting in increased nucleic acid leakage and decreased intracellular DNA content. At 1 × minimum inhibitory concentration (MIC), CA inhibited biofilm formation, with maximum reductions of 76.4 % and 68.3 % for V. parahaemolyticus and V. cholerae, respectively. Molecular dynamics simulations revealed stable binding between CA and critical bacterial proteins except for ompW, with binding energies of -6.6 to -5.8 kcal/mol. RT-qPCR further confirmed downregulation of related gene expression. In shrimp, CA treatment (6 × MIC, 4 h) reduced both Vibrio species by >4.4 log CFU/g. These results demonstrate the potent anti-Vibrio activity of CA, underscoring its potential as a plant-derived antimicrobial agent for ensuring microbial safety in seafood processing industry.

Cis-natural antisense transcript ELENA19 attenuates PAMP-triggered immunity by modulating ABA- and PAMP-inducible UGT71B6 expression, resulting in increased ABA levels and reduced ET-dependent flg22-induced callose deposition in Arabidopsis. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators of various biological processes. However, the roles of lncRNAs in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) remain largely unexplored in plants. Based on our previous custom lncRNA array analysis of Arabidopsis seedlings treated with PAMPs (elf18 and flg22), we identified a novel ELF18-INDUCED LONG NONCODING RNA, ELENA19. In this study, we characterized the function of ELENA19 as a natural antisense transcript of UDP-glycosyltransferase 71B6 (UGT71B6), which is responsible for the glycosylation of abscisic acid (ABA). ELENA19 expression was rapidly upregulated upon treatment with ABA or PAMPs (flg22 and elf18). Among the genes neighboring ELENA19, only UGT71B6 was responsive to both ABA and PAMP treatments. UGT71B6 expression was significantly attenuated in ELENA19-overexpressing (OX) plants compared to wild-type (WT) plants after PAMP or ABA treatment. ELENA19 OX plants were hypersensitive to ABA during germination and had higher endogenous ABA levels than WT plants, suggesting that ELENA19 down-regulates UGT71B6 expression and enhances endogenous ABA levels. Flg22-triggered callose deposition was reduced, and the expression of ethylene (ET)-dependent Flg22-induced genes was significantly down-regulated in ELENA19 OX plants compared to WT plants, confirming the antagonistic interaction between ABA and ET signaling in the flg22-mediated immune response. These results demonstrate that ELENA19 attenuates PAMP-triggered immunity by modulating UGT71B6 expression.

Cholelithiasis has a complex pathogenesis, necessitating better therapeutic and preventive strategies. We recently read with interest Wang et al's study on lysine acetyltransferase 2A (KAT2A)-mediated adenosine monophosphate-activated protein kinase (AMPK) succinylation in cholelithiasis. Using mouse models and gallbladder mucosal epithelial cells, they found that KAT2A inhibits gallstones through AMPK K170 succinylation, thereby activating the AMPK/silent information regulator 1 pathway to reduce inflammation and pyroptosis. This study is the first to connect lysine succinylation with cholelithiasis, offering new insights and identifying succinylation as a potential therapeutic target. Future research should confirm these findings using patient samples, investigate other post-translational modifications, and use structural biology to clarify succinylation-induced conformational changes, thereby bridging basic research to clinical applications.

Globally, liver cancer is the sixth most prevalent cancer type and the third leading cause of cancer-related deaths, making the need for improved treatment evident. We conducted a pan-cancer tissue microarray analysis to identify cancer types with upregulated ribosome biogenesis, potentially suitable for treatment with nucleolar-targeting compounds. Our screening identified liver cancer as a potential candidate. Gene expression analysis confirmed upregulation of nucleolar factors facilitating ribosome biogenesis that correlated with poor prognosis. In hepatocellular carcinoma (HCC) cell lines, constituting around 80% of liver cancer cases, we confirmed the upregulation of the nucleolar proteins Treacle, UBF, and Fibrillarin, involved in transcription and processing of ribosomal RNA (rRNA). Measurements of rRNA also confirmed increased nucleolar activity. We treated the HCC cell lines with nucleolar-targeting compounds and observed increased sensitivity in the HCC cell lines. Notably, nucleolar targeting compounds demonstrated a broader therapeutic window than that observed for Sorafenib, a clinically approved targeted therapy. Furthermore, we investigated how nucleolar factors change during HCC stages and found a progressive increase in Treacle and Fibrillarin in advanced stages of HCC. Our results demonstrate aberrant nucleolar activity in HCC and propose targeting ribosome biogenesis as a therapeutic strategy to improve HCC patient outcomes.