Development of a series of novel potent and selective irreversible covalent FGFR4 inhibitors with a mix-and-match strategy.

Zinc finger proteins, particularly Zinc Finger Protein 706 (ZNF706), have been implicated in various cancers, yet their functional and clinical significance in hepatocellular carcinoma (HCC) remains unclear. Identifying novel biomarkers and therapeutic targets is essential for improving HCC diagnosis and treatment. To investigate the functional role of ZNF706 in HCC and evaluate its potential as a diagnostic and therapeutic target with biotechnological applications. Bioinformatic analyses were performed using clinical and transcriptomic data from TCGA and GTEx databases to assess ZNF706 expression and its correlation with clinicopathological features and patient prognosis. Quantitative PCR and Western blotting validated ZNF706 expression in liver epithelial and HCC cell lines. Functional assays, including CCK-8, flow cytometry, and Transwell migration/invasion assays, were conducted following ZNF706 knockdown. ZNF706 was significantly overexpressed in HCC tissues and cell lines compared to normal controls. High ZNF706 expression correlated with advanced TNM stage, pathological stage, and poor survival outcomes. Knockdown of ZNF706 inhibited proliferation, migration, and invasion, and increased apoptosis in HCC cells. ROC analysis demonstrated high diagnostic accuracy (AUC > 0.90) for ZNF706 in distinguishing HCC and predicting prognosis. ZNF706 is a promising biomarker for HCC diagnosis and prognosis and represents a potential therapeutic target for biotechnological intervention. These findings support the development of ZNF706-based diagnostic assays and targeted therapies for improved management of HCC.

3-Carboxyphenylboronic acid functionalized polydopamine-coated cellulose nanocrystals as a pH-responsive nanocarrier for targeted curcumin delivery.

Nedd4 family interacting protein 1 (NDFIP1) is a novel target of PF-429242 in promoting autophagy in hepatocellular carcinoma cells.

TARDBP upregulates GJB2 to promote tumor progression in hepatocellular carcinoma.

COA6 deficiency inhibits hepatocellular carcinoma progression by regulating cuproptosis through the JAK/STAT signaling pathway.

Molecular regulation and therapeutic targeting of programmed cell death in hepatocellular carcinoma.

The poor prognosis of hepatocellular carcinoma (HCC), especially in advanced stages, underscores the need for new therapeutic strategies. In this study, we show that hyaluronan-mediated motility receptor (HMMR) is highly expressed in HCC tumors compared with normal liver tissues. Knockdown of HMMR using siRNA significantly reduced cell proliferation and migration in both parental and doxorubicin-resistant HCC cell lines without inducing apoptosis. Similarly, treatment with 4-Methylumbelliferone (4-MU), a pharmacological HMMR inhibitor, led to dose-dependent decreases in proliferation and migration in vitro. In vivo, 4-MU treatment significantly inhibited tumor growth in a HepG2 xenograft model, resulting in a 44% reduction in tumor volume by day 20 and an 80% decrease in HMMR expression in tumor tissues. These results demonstrate that HMMR promotes growth and migration in HCC, and targeting HMMR effectively inhibits both parental and drug-resistant HCC cells. Additionally, our findings suggest that 4-MU, an approved drug for biliary tract disorders, holds promise as a repurposed therapeutic candidate for HCC treatment.

Ultrasound-activated piezoelectric BZT Nanocubes mediate direct Piezocatalytic killing and reverse immunosuppressive tumor microenvironment for effective hepatocellular carcinoma therapy.

ASGPR-targeted micelles co-delivering lenvatinib and COP1 siRNA for hepatocellular carcinoma via dual-targeting.

Hepatocellular carcinoma (HCC) represents a major public health issue globally, necessitating the urgent development of new therapies. The therapeutic efficacy of disulfiram (DSF) and copper (Cu) in HCC was investigated in the present study, focusing on cytotoxicity, mitochondrial function, and apoptosis to clarify the mechanistic basis of this drug combination. Our findings revealed a significant, dose-dependent reduction in HCC cell viability with DSF/Cu treatment. Further investigation showed increased reactive oxygen species (ROS) levels, decreased adenosine triphosphate (ATP) production, and a decline in mitochondrial membrane potential (MMP). These events culminated in the activation of caspase-9 and caspase-3, key enzymes in the apoptotic pathway, leading to cell death. Mechanistically, DSF/Cu synergistically increased the expression of activating transcription factor 3 (ATF3), a known tumor suppressor, in HCC cells. In vivo studies using a mouse tumor model supported these findings, demonstrating significantly inhibited tumor growth in the DSF/Cu group compared with the control group. Overall, our study findings suggest that the DSF/Cu combination exhibits significant therapeutic potential against HCC by modulating the ATF3-dependent mitochondrial apoptosis pathway, a strategy that warrants further preclinical exploration.

BAG6 promotes hepatocellular carcinoma growth via enhancing PLK1-mediated aerobic glycolysis.

Multifunctional nano-polymer-based targeted delivery system for CRISPR/Cas9-Mediated hepatocellular carcinoma therapy.

Matrix stiffening-driven hepatocellular carcinoma progression through OASL-mediated cGAS-STING repression and subsequent macrophage activation.

Background: Hypoxia-driven metabolic reprogramming is a hallmark of hepatocellular carcinoma (HCC) and depends critically on mitochondrial signaling. We sought to identify RNA-based molecular factors that orchestrate the hypoxia-mitochondria crosstalk and regulate metabolic adaptation in HCC cells.Methods: An integrated mtRNA-seq and mitochondria-specific LwaCas13a-BN-MLS RNA targeting approach was employed to profile RNA molecules aberrantly enriched in HCC mitochondria. Mitophagy was assessed via mt-Keima assay, immunofluorescence, transmission electron microscopy, and Western blotting of key autophagic markers. RNA-protein interactions were examined using RNA immunoprecipitation (RIP), electrophoretic mobility shift assays (EMSA), and computational structural modeling. In vitro and in vivo tumorigenicity was evaluated using colony formation, transwell invasion, wound healing, and subcutaneous xenograft models in nude mice.Results: Nuclear-encoded EGR1 mRNA was aberrantly translocated to mitochondria, where it functions as a non-translating mRNA (ntmRNA) essential for mitophagy. Mitochondria-specific EGR1 targeting disrupted mitochondrial homeostasis by accumulating damaged mitochondria, lowering ATP, increasing ROS, reducing membrane potential, diminishing spare respiratory capacity, and impairing hypoxia-induced mitophagy. Mechanistically, EGR1 ntmRNA promoted mitophagy through the HIF-1α/BNIP3/NIX axis by recruiting BNIP3 to mitochondria and coordinating its homodimerization via a 3′-UTR MRE. A synthetic MRE oligonucleotide rescued BNIP3 dimerization after EGR1 depletion. Finally, we demonstrated that EGR1 loss suppressed malignant phenotypes in vitro and reduced xenograft tumor growth in vivo.Conclusions: This study reveals a noncanonical role for EGR1 mRNA as an epigenetic regulator of mitophagy in HCC, thus expanding the functional repertoire of mRNA molecules beyond protein coding. Targeting this noncanonical EGR1 ntmRNA-BNIP3 homodimerization mechanism may suggest new therapeutic strategies for treating HCC.

Therapeutic effects of the n-butanol extract of Potentilla freyniana Bornm. in hepatocellular carcinoma cells.

Multispectral imaging flow cytometry identifies the formation of polyploid giant cancer cells and cellular senescence induced by CD147 depletion.

Novel senescence inducer ICA-11c, a derivative of icaritin, YAP-dependently suppresses hepatocellular carcinoma cells.

[This retracts the article DOI: 10.3727/096504017X14850151453092.].

Triptolide impacts CSF1R expression and reprograms the suppressive function of myeloid-derived suppressor cells via targeting the ER stress pathway.