Kibdelomycin and kibdelomycin A are antibiotics biosynthesized by Kibdelosporangium banguiense CA-240109. Kibdelomycin demonstrates broad-spectrum activity, exhibiting significant activity against antibiotic-resistant Gram-positive bacteria. These compounds inhibit DNA GyrB and ParE through a distinct U-shaped multi-contact binding mechanism and do not display cross-resistance with established antibiotics. To investigate structure-activity relationships, various methodologies were employed to identify new congeners, including the implementation of repeat batch fermentation. This study presents the discovery, isolation, structural elucidation, and antibacterial assessment of two mono des-chloro congeners of kibdelomycin A produced via repeat batch fermentation. The newly discovered compounds displayed inhibitory effects on bacterial growth in Staphylococcus aureus and Escherichia coli, with minimum inhibitory concentrations (MIC) ranging from 16 to 64 μg/mL. The MIC values for E. coli are comparable to kibdelomycin, whereas for S. aureus the MIC is 64 times less potent than that of kibdelomycin. AI-assisted docking studies involving DNA gyrase B enzymes provide reasonable support for varying activities of the congeners.

Conotoxins, isolated from the venom produced by marine snails of the Conus genus, are a range of bioactive, disulfide-rich peptides. However, their narrow therapeutic window and significant interindividual variability make the efficient and accurate detection of their concentration in biological fluids a "lifeline" for ensuring safe and effective clinical use. In this work, we employed α-conotoxin ImI (α-ImI) and ziconotide as model peptides. Inspired by the mechanisms through which these two peptides exert bioactivity, we fabricated and characterized porous polystyrene-based magnetic microspheres grafted with a terpolymer, poly (divinylbenzene-co-N-vinylpyrrolidone-co-vinylphosphonic acid), DVB-co-NVP-co-VPA, for the efficient capture of α-ImI and ziconotide from biofluid samples. The results implied that the modified DVB-co-NVP-co-VPA enhanced the selectivity and adsorption capability for α-ImI and ziconotide. The established method was characterized by good linearity (R2 above 0.9993), acceptable sensitivity (LODs below 0.03 μg mL-1), high accuracy (recoveries ranging from 85.3% to 92.9%) and excellent repeatability (RSDs varied from 1.3% to 2.8%). Furthermore, the adsorbent maintained good reusability over six adsorption-desorption cycles, indicating its potential as an efficient candidate for pharmacokinetic studies of conotoxins.

Precise monitoring of formaldehyde (FA) in biological, food, and environmental systems is of considerable importance due to its toxicity, high volatility, and illegal use as a preservative in certain food-related matrices. Herein, a novel near-infrared (NIR) fluorescent probe (abbreviated as DCI-FA) for FA with ultralow detection limit and high sensitivity as well as favorable selectivity was presented. DCI-FA enabled real-time visualization of exogenous FA in living cells and zebrafish, and successfully tracked tetrahydrofolate-induced endogenous FA fluctuations. Notably, DCI-FA also represented a fluorescent probe that applied to sensitive detection and fluorescence imaging of FA residues in food-medicine homology samples. Moreover, a mesoporous silica-loaded fluorescent probe (as referred to DCI-FA) was successfully constructed to on-site monitor environmental FA gas even in ppm-level. Overall, this work established a versatile NIR fluorescent sensing platform for FA detection with promising applications in biological imaging, food safety assessment, and environmental hazardous gas analysis.

G protein-coupled receptors (GPCRs) serve as central hubs in tumor signal transduction and microenvironment regulation. However, their therapeutic exploitation is confounded by a fundamental complexity: GPCR functions are exquisitely context-dependent, varying across cell types and spatial locations within the heterogeneous tumor microenvironment. A single receptor may drive malignant proliferation while simultaneously recruiting immunosuppressive cells, and pathways inhibited by small molecules can be reactivated through parallel axes. This multidimensional regulatory conundrum renders conventional single-axis inhibition strategies inherently limited. This review systematically examines the distribution and pathological functions of tumor-associated GPCRs, critically analyze why current mainstream modalities often fail in the TME context, and spotlight next-generation strategies such as allosteric modulation, targeted protein degradation, nucleic acid therapeutics, and engineered cell therapies that are uniquely poised to actively modulate the TME in a context-aware manner. By integrating enabling technologies including artificial intelligence, cryo-electron microscopy, and organoid models, we chart a transformative path from single-axis inhibition toward multi-dimensional regulation, ultimately advancing more durable cancer therapies.

The combination of anti-PD-L1 and paclitaxel (PTX) is a standard-of-care regimen for triple-negative breast cancer (TNBC). However, TNBC is classified as a ″cold″ tumor characterized by low immunogenicity, hypoxia, and the aberrant activation of signal transducer and activator of transcription 3 (STAT3), which greatly reduces the efficacy of immune checkpoint blockades (ICBs). This project aims to construct an albumin-based nanomedicine coloaded with atovaquone (ATO) and PTX for targeted tumor delivery, thereby enhancing the therapeutic efficacy of ICBs. The nanomedicine exhibits optimal particle size, exceptional stability, excellent biocompatibility, and a high drug encapsulation efficiency. Among these, ATO enhances PTX-induced immunogenic cell death by alleviating tumor hypoxia, thereby increasing tumor immunogenicity. Furthermore, ATO reduces STAT3 phosphorylation, modulating the immunosuppressive tumor microenvironment. The combination of nanomedicine with ICBs synergistically transforms TNBC from an immunologically ″cold″ to a ″hot″ tumor. This transformative approach significantly enhances the therapeutic efficacy of combination chemotherapy, leading to potent suppression of primary tumors while concurrently preventing postoperative recurrence and pulmonary metastases. This project has the potential to introduce innovative strategies and methodologies aimed at overcoming the limited efficacy of PTX combined with ICBs in the treatment of TNBC.

The resistance of non-small cell lung cancer (NSCLC) to Paclitaxel (PTX) stems from the enhanced drug efflux mediated by ATP-binding cassette (ABC) transporters and the upregulated PARP1-dependent DNA repair pathway. To address this challenge, the present study constructed a self-assembled nanoprodrug, PSOTNs, featuring covalent conjugation of three therapeutic agents. Structurally, PTX was functionalized with a disulfide bond to confer GSH-responsive release, whereas Olaparib (OLP) was tethered via a thioketal linker for ROStriggered liberation, and tetramethylpyrazine (TMP) was hydrophobically modified to drive self-assembly and facilitated mitochondria-specific targeting under acidic conditions. The delicate PSOTNs exhibited high drug loading, favorable colloidal stability, and enhanced tumor accumulation via the EPR effect. Upon cellular internalization, the elevated GSH level prompted rapid release of PTX, effectively inhibiting microtubule dynamics. Concurrently, TMP-mediated mitochondrial enrichment and the subsequent ROS-triggered cleavage released OLP along with cinnamaldehyde, which synergistically amplified oxidative stress, induced mitochondrial dysfunction, and suppressed P-glycoprotein-mediated drug efflux. In vitro assays demonstrated that PSOTNs significantly enhanced drug accumulation, induced DNA damage, provoked G2/M cell cycle arrest, and promoted apoptosis, outperforming both individual agents and the non-responsive control. Furthermore, PSOTNs revealed potent tumor growth inhibition in A549/Tax xenograft models, prolonged systemic circulation, and excellent biocompatibility. In summary, PSOTNs represent a novel nanotherapeutic strategy that overcomes PTX resistance through a triple synergistic mechanism of "microtubule disruption-DNA repair inhibition-mitochondrial function intervention," offering a promising paradigm for the treatment of drug-resistant malignancies.

Ulcerative colitis (UC) is the most common chronic inflammatory disease of the intestinal tract in clinical practice, and long-term chronic inflammation leads to repeated damage to and repair of the colonic mucosa, which may progress to malignancy through atypical hyperplasia. However, there are currently no fully targeted drugs for the treatment of UC. In this review, we discuss several cellular processes, such as autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, macrophage polarization, ferroptosis and the Th/Treg cell balance, which are associated with the occurrence and development of UC. Many molecular targets and signaling pathways, such as nuclear factor kappa-B (NF-κB), phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), Wnt/β-catenin, adenosine 5’-monophosphate-activated protein kinase (AMPK), toll-like receptor (TLR), Janus kinase/signal transducer and activator of transcription (JAK/STAT), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs), play crucial roles in the progression of UC. We also summarize the common treatment strategies for UC, including lifestyle interventions, aminosalicylic acid preparations, corticosteroid drugs, biologics, fecal microbiota transplantation, and other drugs for symptomatic treatment. This review provides a detailed theoretical basis for the pathology and treatment of UC. Future research could focus on optimizing the treatment plan and achieving more precise and personalized treatment with multiple targets in multiple aspects.

Rationale:Non-small cell lung cancer (NSCLC) develops a high GSH/GPX4 antioxidant phenotype under persistent oxidative pressure, which suppresses membrane lipid peroxidation and ferroptosis, constituting a core mechanism underlying chemotherapy resistance and suboptimal therapeutic efficacy. Breaking this resistance barrier demands not simply attacking the tumor but disarming the antioxidant defense to intensify oxidative damage and awaken durable antitumor immunity. Methods:A self-assembled nano-prodrug, E-R@ISSL, was engineered by co-assembling a carbamate-linked RGD-modified etoposide (ETP) prodrug and a disulfide-bonded indole derivative conjugated to linoleic acid (LA) at an optimal 1:2 molar ratio. The system thus possesses dual αvβ5/mitochondria targeting with CES2/GSH cascade-responsive drug release. Antitumor activity and mechanisms were evaluated in vitro and in both subcutaneous and orthotopic NSCLC mouse models. Results:E-R@ISSL exhibited efficient αvβ5-mediated internalization and mitochondria-targeted delivery. Upon sequential CES2/GSH-triggered disassembly, E-R@ISSL co-released ETP and LA, reduced the available intracellular GSH pool, and functionally dampened the GSH-dependent GPX4 antioxidant defense. ETP induced DNA double-strand breaks and elevated reactive oxygen species (ROS), while LA expanded the oxidizable lipid pool, synergistically driving lipid peroxidation and ferroptosis. Concurrently, the system activated immunogenic cell death (ICD), promoting dendritic cell maturation and enhancing CD8+ T cell infiltration. In orthotopic NSCLC models, E-R@ISSL significantly suppressed tumor progression, prolonged survival, and demonstrated a favorable safety profile with reduced systemic toxicity compared with free ETP. Conclusions:Together, these findings demonstrate that E-R@ISSL achieved coordinated DNA damage, ferroptosis, and ICD induction through its dual-targeted and sequentially activated co-delivery of ETP and LA, concurrently dismantling the GSH/GPX4 antioxidant defense and intensifying oxidative injury. This nano-prodrug thus represents a viable strategy for overcoming treatment resistance and extending durable antitumor responses in NSCLC.

Abstract Although there have been recent advancements in immune checkpoint inhibitors (ICIs) for gastric cancer (GC), pinpointing the essential T‐cell subsets that drive antitumor responses continues to pose a challenge. In this study, we created a coculture system using patient‐derived organoids (PDOs) and tumor‐infiltrating lymphocytes (TILs) that mimics important interactions between PDOs and TILs in the presence of various ICIs. Our findings reveal that CD62L+ T cells, activated by CD44+ cancer stem cells (CSCs), facilitate tumor regression in samples sensitive to ICIs. Additionally, publicly available single‐cell RNA sequencing (scRNA‐seq) data indicate that stem‐like SELL+ T cells, which show increased expression of DHX58, enhance their interactions with CD44+ CSCs in GC patients who have favorable prognoses. This research highlights the promise of DHX58+ SELL+ T cells, in a stem‐like state prompted by CD44+ CSCs, as potential diagnostic markers and targets for T cell‐based immunotherapy in GC.

The fruit of Choerospondias axillaris is commonly used in the food industry for producing candies and cakes. However, limited research on polysaccharides from C. axillaris fruit has restricted their application. In this study, a homogeneous pectic polysaccharide of 22.4 kDa, designated as CAP-3, was isolated from C. axillaris fruit. Structural characterization revealed that CAP-3 exhibited a backbone composed of consecutive 1,4-α-GalpA residues and alternating disaccharide units of 1,2-α-Rhap and 1,4-α-GalpA, with DM of 8.4% and DA of 0.05%. The side chains consisted of 1,6-β-Galp and 1,5-α-Araf linked to C-3 of GalpA, as well as T-β-Galp and T-α-GalpA residues attached to C-4 of Rha. To explore its application potential, the encapsulation performance of CAP-3 was evaluated using two representative food bioactives, resveratrol and astragaloside IV, as model compounds. Accordingly, RES@CAP-3-Mg2+ (RES:CAP-3, 1: 4, w/w) and AS-IV@CAP-3-zein (AS-IV:zein:CAP-3, 1: 10: 5, w/w/w) complexes were successfully constructed via different assembly mechanisms. Both complexes exhibited favorable physicochemical properties, including uniform particle size distributions (369.6 nm and 397.6 nm), spherical morphology, spectral features, and improved stability. These findings demonstrated that CAP-3 is a potential natural pectin-based delivery medium for encapsulating functional ingredients, thereby expanding the applications of C. axillaris in the food field.

Benzoic acid (BA) and acesulfame K (ACE) are commonly co-present food additives, yet their combined nephrotoxic risk remains poorly understood. Employing network toxicology, molecular simulations, and in vitro assays, we systematically evaluated their individual and combined effects on nephrotoxicity. Computational predictions indicated that both compounds exhibited nephrotoxic propensity, with shared targets enriched in pathways such as "response to xenobiotic stimulus" and metabolic disruption. Protein-protein interaction network analysis identified CTNNB1 and STAT3 as the respective core targets for BA and ACE, with molecular simulations confirming their stable binding. In vitro experiments showed that BA alone inhibited HK2 cell proliferation, and downregulated β-catenin (encoded by CTNNB1). ACE alone did not significantly suppress proliferation but activated STAT3 signaling. Notably, combined exposure produced a marked synergistic anti-proliferative effect, attributable to a dual mechanism: BA impaired renal tubular repair capacity by suppressing the CTNNB1/β-catenin pathway, while ACE exacerbated inflammatory and injury responses via STAT3 activation, thereby simultaneously impairing repair and exacerbating damage in the kidney. This study is the first to reveal that BA and ACE have the potential to synergistically induce nephrotoxicity via the CTNNB1/STAT3 signaling axis, providing new scientific evidence for the systematic safety assessment of mixed food-additive exposures.

Aberrant activation of macrophages and their amplification of inflammatory responses constitute the core pathological basis driving the progression of acute lung injury (ALI). Celastrol (CE), despite its potent anti-inflammatory activity, suffers from poor aqueous solubility and substantial systemic toxicity, which severely limit its clinical translation. Capitalizing on the metabolic signature of pro-inflammatory M1 macrophages, specifically their high expression of glucose transporter 1 (GLUT1), we designed a glucose-modified CE prodrug that self-assembled into carrier-free nanoparticles CG NPs. With markedly improved solubility and systemic stability, CG NPs rapidly and persistently accumulated in the inflammatory lungs of LPS-induced ALI mice facilitated by GLUT1-mediated targeting and uptake by M1 macrophages. Compared with free CE, CG NPs exhibited enhanced overall therapeutic efficacy while significantly reducing hepatorenal toxicity. Mechanistic studies revealed that by targeting Drp1, CG NPs disrupt Drp1-MiD51 interaction, thus inhibiting excessive mitochondrial fission and ROS accumulation, which blocks NF-κB-mediated inflammatory signaling and M1-driven cytokine release. Molecular docking suggested that glucose conjugation may confer CG with a superior ability to regulate mitochondrial homeostasis over CE, potentially driven by its unique U-shaped conformation that inserts into Drp1 and forms a denser hydrogen-bond network, which could contribute to enhanced binding affinity. In summary, this study proposes a nanoprodrug strategy that combines precise targeting with mitochondrial protection, offering a promising therapeutic avenue for inflammatory diseases such as ALI.

Interference with calcium homeostasis provokes tumor cell death and immune response, providing a novel direction for tumor immunotherapy as a promising cancer treatment strategy. Nevertheless, most reported Ca2+-overloaded nanoinducers encounter challenges such as intricate preparation procedures, safety concerns arising from inorganic material input, and limited anti-tumor efficiency. Herein, we synthesized a biocompatible and pH-sensitive Ca-doped cyclodextrin metal-organic framework (Ca/K-MOF) as a carrier, which was then loaded with photosensitizer hypericin (HY) via a simple one-pot synthesis to form HY@Ca/K-MOF. To enhance the stability both in vitro and in vivo, we coated HY@Ca/K-MOF with a hydrophilic layer of PEG (PEGHY@Ca/K-MOF). When exposed to 590 nm photoirradiation, PEGHY@Ca/K-MOF, with its pH-responsive dissociation, the Ca2+and HY mediators released at the tumor site share the responsibility of triggering intracellular Ca2+disturbances, which amplified the production of reactive oxygen species (ROS) and led to mitochondrial calcium overload through modulating mitochondrial MICU1 function. Under photocontrol, this interplay between ROS generation and mitochondrial calcium overload created a bidirectional amplification effect, where each process reinforced the other, subsequently eliciting a pyroptosis-evoked immune response. Significantly, this newly constructed delivery platform effectively suppressed both primary and distant tumors without the need for additional immunological interventions. In summary, this Ca2+-doped MOF-based nanomaterial provides a promising approach for efficient tumor photo-controlled mitochondrial Ca2+ overloadpyroptosis immunotherapy. 2025 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Antibiotics remain the conventional mainstay for acute local inflammation, such as pharyngitis, but concerns over bacterial resistance, superinfections, and hepatorenal toxicity have driven research toward natural alternatives. Methyl salicylate (SAM) and L-menthol (MENT), derived from medicinal plants, exhibit anti-inflammatory, analgesic, and antimicrobial properties. However, their clinical translation is hampered by inadequate synergy, rapid metabolism, and low bioavailability in existing formulations. To overcome these issues, we synthesized an ROS-responsive prodrug, SSM, by conjugating SAM and MENT via a sulfide bond, and further encapsulated it within hydroxypropyl-β-cyclodextrin (HP-β-CD) to form HP-β-CD@SSM. This complex enabled targeted drug release in high-ROS inflammatory microenvironments, enhancing local bioavailability and reducing systemic exposure. The use of HP-β-CD not only enhanced the water solubility and stability of SSM but also masked the unpleasant odor of the drugs, thereby improving patient compliance. In vitro and in vivo studies demonstrated that HP-β-CD@SSM effectively disrupts the vicious cycle of inflammation and oxidative stress through synergistic inhibition of the NF-κB pathway and activation of the Nrf2 pathway, resulting in significantly enhanced anti-inflammatory and analgesic effects in both pharyngitis and paw edema models, with no observable systemic toxicity. This work presents not only a promising therapeutic candidate for pharyngitis but also a robust localized drug delivery strategy for natural products with considerable translational value.

Polystyrene microplastics (PS-MPs) are ubiquitous environmental contaminants that pose a significant threat to ecosystems and human health. The toxicity of PS-MPs to the liver is associated with a surge of reactive oxygen species (ROS). However, the specific type of ROS triggered by PS-MPs in the injured liver tissue remains inadequately known. In this study, a dual-channel near-infrared (NIR) fluorescent probe TPAC-B with distinct aggregation-induced emission (AIE) properties was contructed, which can specifically detect HOCl and target dual organelles (mitochondria and lipid droplets). Firstly, TPAC-B exhibited selective detection of HOCl with dual-channel imaging in PS-MPs-treated cells, thus eliciting a 40-fold ratiometric fluorescence enhancement. Probe TPAC-B was also prone to accumulate in the liver, and real-time monitoring of elevated HOCl levels in a mouse model of PS-MPs-induced liver injury was thus achieved. As confirmed by western blot analysis, PS-MPs could suppress the expression of ferroptosis regulatory proteins glutathione peroxidase 4 (GPX4) and Ferritin in liver cells and upregulate the expression of heme oxygenase-1 (HO-1, a marker protein for oxidative stress). Therefore, the work shown here represents the first fluorescent probe capable of tracking the fluctuation of HOCl levels in PS-MPs-induced liver injury, providing a potent imaging tool for the early diagnosis of this disease.

BackgroundClinical evidence demonstrates that induction differentiation therapy is a useful treatment strategy for melanoma. Circular RNAs (circRNAs) plays a crucial role in melanoma cell proliferation, resistance and metastasis. However, the roles of circRNAs during melanoma cell differentiation have not been fully investigated. This study aimed to investigate the role and mechanism of circSipa1l1 in melanoma cell differentiation.MethodsAll-trans-retinoic acid (ATRA) or sodium phenylbutyrate-4 (PB-4) were employed to induce melanoma B16 cells differentiation, and whole transcriptome sequencing was performed to screen for differentially expressed circRNAs. RNA stability assay, quantitative real-time polymerase chain reaction (qRT-PCR), tissue microarray and fluorescence in situ hybridization (FISH) was employed to confirm the existence, expression level and subcellular localization of circSipa1l1. Cell counting kit-8 (CCK-8), colony formation, cell cycle analysis, melanin content, tyrosinase activity assay, RNA pull-down, RNA immunoprecipitation (RIP) and western blotting were used to evaluate the effect of circSipa1l1 on melanoma cell differentiation and explore its regulatory mechanism. Finally, mouse xenograft models were used to assess the effect of circSipa1l1 silencing on tumor growth in vivo.ResultsCircSipa1l1 was significantly downregulated in ATRA- or PB-4-treated B16 cells and highly expressed in melanoma patient tissues. Silencing circSipa1l1 induced cell-cycle arrest and differentiation in melanoma A375 and B16 cells, while its overexpression promoted proliferation. Mechanistically, circSipa1l1 directly interacts with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), a key RNA-binding protein. Silencing circSipa1l1 inhibited the IGF2BP1 and rho GDP-dissociation inhibitor 2 (ARHGDIB) mRNA interaction, destabilizing ARHGDIB mRNA and subsequently inhibiting the extracellular signal-regulated kinase (ERK) signaling pathway-ultimately inducing differentiation and repressing cell cycle progression. Furthermore, silencing circSipa1l1 significantly inhibited tumor growth in both B16 and A375 xenograft models.ConclusionOur findings reveal that circSipa1l1 acts as an oncogenic circRNA by regulating the IGF2BP1/ARHGDIB/ERK axis in melanoma, suggesting it could be a potential therapeutic target for melanoma differentiation therapy.

Doxorubicin (Dox) is a highly effective antitumor drug with established therapeutic benefits across various tumor types, whose non-negligible and potent side effect is the Dox-induced cardiotoxicity (DIC). Early diagnosis of DIC is difficult, and available therapeutic regimens are quite limited. Inspired by the unique structure and efficient anti-DIC bioactivity of the natural compound tanshinone IIA (Tan IIA), we rationally developed its fluorescently emissive analogue TOP with preserved anti-DIC efficacy. Especially, TOP was fabricated into a hydrogen peroxide (H2O2)-responsive prodrug TOP-B, which could be activated by the oxidation stress during DIC, thereby facilitating the simultaneous fluorescence monitoring and treatment of DIC. Specifically, monitoring the fluctuation of H2O2 with the probe TOP-B can directly reflect the progression of DIC in the cardiomyocyte, zebrafish, and mouse models. TOP-B can also promote the expression of antioxidant proteins, which contribute to the alleviation of DIC. Needless to say, probe TOP-B not only serves as a promising therapeutic drug and fluorescence-guided imaging agent for DIC, but more importantly provides inspiration to construct other rationally designed theranostic probes derived from the natural product skeletons for specific diseases.

Growing research indicates that long noncoding RNAs (lncRNAs) are pivotal in the development and advancement of hepatocellular carcinoma (HCC). Our research pinpointed LINC01547 as a notable lncRNA that was significantly downregulated in Hep3B cells treated with bufotalin, whereas it exhibited elevated expression levels in HCC tumor tissues. Further study found that silencing LINC01547 markedly suppressed proliferation, induced apoptosis, and inhibited migration and invasion in Hep3B and HepG2 cells. LINC01547 knockdown reduced ADAR1 expression, which led to apoptosis and suppressed metastasis via inhibition of the FAK signaling pathway. Additionally, silencing LINC01547 upregulated miR-146b-5p, which in turn decreased RAC1 levels, further promoting apoptosis and inhibiting metastasis in HCC cells. In vivo, a Hep3B tumor-bearing mouse model confirmed the antitumor effects of LINC01547 silencing. Our findings demonstrate that LINC01547 regulates HCC cell apoptosis and metastasis through the ADAR1/FAK and miR-146b-5p/RAC1 pathways, suggesting that LINC01547 may serve as a biomarker and potential therapeutic target for HCC.