Integrating single-cell and multi-omic approaches reveals Euphorbiae Humifusae Herba-dependent mitochondrial dysfunction in non-small-cell lung cancer.

Euphorbiae Humifusae Herba (EHH) is a pivotal therapeutic agent with diverse pharmacological effects. However, a substantial gap exists in understanding its pharmacological properties and anti-tumour mechanisms. This study aimed to address this gap by exploring EHH's pharmacological properties, identifying NSCLC therapy-associated protein targets, and elucidating how EHH induces mitochondrial disruption in NSCLC cells, offering insights into novel NSCLC treatment strategies. String database was utilized to explore protein-protein interactions. Subsequently, single-cell analysis and multi-omics further unveiled the impact of EHH-targeted genes on the immune microenvironment of NSCLC, as well as their influence on immunotherapeutic responses. Finally, both in vivo and in vitro experiments elucidated the anti-tumour mechanisms of EHH, specifically through the assessment of mitochondrial ROS levels and alterations in mitochondrial membrane potential. EHH exerts its influence through engagement with a cluster of 10 genes, including the apoptotic gene CASP3. This regulatory impact on the immune milieu within NSCLC holds promise as an indicator for predicting responses to immunotherapy. Besides, EHH demonstrated the capability to induce mitochondrial ROS generation and perturbations in mitochondrial membrane potential in NSCLC cells, ultimately leading to mitochondrial dysfunction and consequent apoptosis of tumour cells. EHH induces mitochondrial disruption in NSCLC cells, leading to cell apoptosis to inhibit the progress of NSCLC.

A flexible self-supported electrochemical sensor Co-NC/PS@CC for real-time detection of cell-released H2O2.

BACKGROUND: Hydrogen peroxide (H2O2) is an important reactive oxygen species (ROS) molecule involved in cell metabolism regulation, transcriptional regulation, and cytoskeleton remodeling. Real-time monitoring of H2O2 levels in live cells is of great significance for disease prevention and diagnosis. RESULTS: We utilized carbon cloth (CC) as the substrate material and employed a single-atom catalysis strategy to prepare a flexible self-supported sensing platform for the real-time detection of H2O2 secreted by live cells. By adjusting the coordination structure of single-atom sites through P and S doping, a cobalt single-atom nanoenzyme Co-NC/PS with excellent peroxidase-like activity was obtained. Furthermore, we explored the enzyme kinetics and possible catalytic mechanism of Co-NC/PS. Due to the excellent flexibility, high conductivity, strong adsorption performance of carbon cloth, and the introduction of non-metallic atom-doped active sites, the developed Co-NC/PS@CC exhibited ideal sensing performance. Experimental results showed that the linear response range for H2O2 was 1-17328 µM, with a detection limit (LOD) of 0.1687 µM. Additionally, the sensor demonstrated good reproducibility, repeatability, anti-interference, and stability. SIGNIFICANCE: The Co-NC/PS@CC prepared in this study has been successfully applied for detecting H2O2 secreted by MCF-7 live cells, expanding the application of single-atom nanoenzymes in live cell biosensing, with significant implications for health monitoring and clinical diagnostics.

MiR-2110 induced by chemically synthesized cinobufagin functions as a tumor-metastatic suppressor via targeting FGFR1 to reduce PTEN ubiquitination degradation in nasopharyngeal carcinoma.

Tumor cell metastasis is the key cause of death in patients with nasopharyngeal carcinoma (NPC). MiR-2110 was cloned and identified in Epstein-Barr virus (EBV)-positive NPC, but its role is unclear in NPC. In this study, we investigated the effect of miR-2110 on NPC metastasis and its related molecular basis. In addition, we also explored whether miR-2110 can be regulated by cinobufotalin (CB) and participate in the inhibition of CB on NPC metastasis. Bioinformatics, RT-PCR, and in situ hybridization were used to observe the expression of miR-2110 in NPC tissues and cells. Scratch, Boyden, and tail vein metastasis model of nude mouse were used to detect the effect of miR-2110 on NPC metastasis. Western blot, Co-IP, luciferase activity, colocalization of micro confocal and ubiquitination assays were used to identify the molecular mechanism of miR-2110 affecting NPC metastasis. Finally, miR-2110 induced by CB participates in CB-stimulated inhibition of NPC metastasis was explored. The data showed that increased miR-2110 significantly suppresses NPC cell migration, invasion, and metastasis. Suppressing miR-2110 markedly restored NPC cell migration and invasion. Mechanistically, miR-2110 directly targeted FGFR1 and reduced its protein expression. Decreased FGFR1 attenuated its recruitment of NEDD4, which downregulated NEDD4-induced phosphatase and tensin homolog (PTEN) ubiquitination and degradation and further increased PTEN protein stability, thereby inactivating PI3K/AKT-stimulated epithelial-mesenchymal transition signaling and ultimately suppressing NPC metastasis. Interestingly, CB, a potential new inhibitory drug for NPC metastasis, significantly induced miR-2110 expression by suppressing PI3K/AKT/c-Jun-mediated transcription inhibition. Suppression of miR-2110 significantly restored cell migration and invasion in CB-treated NPC cells. Finally, a clinical sample assay indicated that reduced miR-2110 was negatively correlated with NPC lymph node metastasis and positively related to NPC patient survival prognosis. In summary, miR-2110 is a metastatic suppressor involving in CB-induced suppression of NPC metastasis.

Alkaloid-metabolites from the mangrove-derived fungus Penicillium robsamsonii HNNU0006.

Nine metabolites, including three undescribed alkaloids pyripyropenes VW (1-2), penicioxa A (4), two previously reported pyripyropene A (3), oxaline (5), three grisephenone-type xanthone derivatives (6-8), and a diphenyl ether derivative 4-chloro-7,4'-dihydroxy-5,2'-dimethoxy-2-methylformate-6'-methybenzophone (9), were isolated from cultures of the mangrove-derived fungus Penicillium robsamsonii HNNU0006. Their structures were determined by spectroscopic analysis, ECD calculations, together with DP4+ probability analysis. Furthermore, all the isolated compounds were tested for cytotoxicity and anti-phytopathogenic fungal activities. Compounds 6-8 showed moderate cytotoxicity against tumor cell lines A549, with IC50 values ranging from 5.68 ± 0.21 to 9.71 ± 0.34 µg/mL, respectively.

Therapeutic role of neural stem cells in neurological diseases.

The failure of endogenous repair is the main feature of neurological diseases that cannot recover the damaged tissue and the resulting dysfunction. Currently, the range of treatment options for neurological diseases is limited, and the approved drugs are used to treat neurological diseases, but the therapeutic effect is still not ideal. In recent years, different studies have revealed that neural stem cells (NSCs) have made exciting achievements in the treatment of neurological diseases. NSCs have the potential of self-renewal and differentiation, which shows great foreground as the replacement therapy of endogenous cells in neurological diseases, which broadens a new way of cell therapy. The biological functions of NSCs in the repair of nerve injury include neuroprotection, promoting axonal regeneration and remyelination, secretion of neurotrophic factors, immune regulation, and improve the inflammatory microenvironment of nerve injury. All these reveal that NSCs play an important role in improving the progression of neurological diseases. Therefore, it is of great significance to better understand the functional role of NSCs in the treatment of neurological diseases. In view of this, we comprehensively discussed the application and value of NSCs in neurological diseases as well as the existing problems and challenges.

Efficacy and safety of anlotinib plus anti-PD-1 agents in patients with refractory advanced biliary tract cancers.

BACKGROUND: Anlotinib has demonstrated promising anti-tumor efficacy in various solid tumors. Additionally, there is evidence suggesting that immune therapy can enhance the systemic responses of anlotinib. This study aimed to assess the effectiveness and safety of combining anlotinib with PD-1 inhibitors compared to fluoropyrimidine-based chemotherapy as a second-line treatment option for advanced biliary tract cancers (BTCs). METHODS: A total of 242 patients with BTCs were screened at the First Affiliated Hospital of Zhengzhou University from October 2015 to October 2022. Among them, 78 patients who received either anlotinib plus PD-1 inhibitors (AP) or fluoropyrimidine-based chemotherapy (FB) as second-line treatment were included in the study. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), safety, and predictive tumor biomarkers. RESULTS: Among the 78 patients with BTCs, 39 patients received AP, while 39 patients were administered FB. The ORR in the AP group was 20.5%, compared to 5.1% in the FB group. The DCR was 87.2% in the AP group and 66.7% in the FB group. The AP group demonstrated significantly better ORR and DCR compared to the FB group (p = 0.042, p = 0.032). The median PFS and OS in the AP group were 7.9 months (95% CI: 4.35-11.45) and 13.9 months (95% CI: 5.39-22.41), respectively. In the FB group, the median PFS and OS were 4.1 months (95% CI: 3.17-5.03) and 13.2 months (95% CI: 8.72-17.68), respectively. The AP group exhibited significantly better median PFS than the FB group (p = 0.027). In the subgroup analysis, patients without liver metastasis had a much longer PFS in the AP group compared to the FB group (14.3 vs. 5.5 months, p = 0.016). Similarly, patients with CEA ≤ 5 µg/L also demonstrated a longer PFS in the AP group compared to the FB group (8.7 vs. 3.9 months, p = 0.008). CONCLUSIONS: The combination of anlotinib and PD-1 inhibitors demonstrated a promising clinical effect compared to fluoropyrimidine-based chemotherapy in the second-line treatment of refractory advanced BTCs. Liver metastases and CEA levels may serve as predictive factors for identifying patients who may benefit from AP therapy.

Deciphering ACE2-RBD binding affinity through peptide scanning: A molecular dynamics simulation approach.

Rapid discovery of target information for protein-protein interactions (PPIs) is significant in drug design, diagnostics, vaccine development, antibody therapy, etc. Peptide microarray is an ideal tool for revealing epitope information of PPIs. In this work, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) and the host cell receptor angiotensin-converting enzyme 2 (ACE2) were introduced as a model to study the epitope information of RBD-specific binding to ACE2 via a combination of theoretical calculations and experimental validation. Through dock and molecular dynamics simulations, it was found that among the 22 peptide fragments that consist of RBD, #14 (YNYLYRLFRKSNLKP) has the highest binding strength. Subsequently, the experiments of peptide microarray constructed based on plasmonic materials chip also confirmed the theoretical calculation data. Compared to other methods, such as phage display technology and surface plasmon resonance (SPR), this method is rapid and cost-effective, providing insights into the investigation of pathogen invasion processes and the timely development of peptide drugs and other fields.

A Self-Homing and Traceable Cardiac Patch Leveraging Ferumoxytol for Spatiotemporal Therapeutic Delivery.

Mesenchymal stem cell (MSC)-based cardiac patches are envisioned to be a promising treatment option for patients with myocardial infarction. However, their therapeutic efficacy and duration are hampered due to their limited retention on the epicardium. We engineered a scaffold-free MSC sheet with an inherent ability to migrate into the infarcted myocardium, a strategy enabled by actively establishing a sustained intracellular hypoxic environment through the endocytosis of our FDA-approved ferumoxytol. This iron oxide nanoparticle stabilized hypoxia-induced factor-1α, triggering upregulation of the CXC chemokine receptor and subsequent MSC chemotaxis. Thus, MSCs integrated into 2/3 depth of the left ventricular anterior wall in a rat model of acute myocardial infarction and persisted for at least 28 days. This led to spatiotemporal delivery of paracrine factors by MSCs, enhancing cardiac regeneration and function. Ferumoxytol also facilitated the noninvasive MRI tracking of implanted MSCs. Our approach introduces a strategy for mobilizing MSC migration, holding promise for rapid clinical translation in myocardial infarction treatment.

Wearable electrochemical patch based on iron nano-catalysts incorporated laser-induced graphene for sweat metabolites detection.

The development of wearable devices shows great application potential in health management. In this work, we propose the fabrication of a novel wearable electrochemical patch and prove its application in sweat metabolites detection. The patch is developed based on iron nano-catalysts incorporated laser-induced graphene (FeNCs/LIG), which is a newly integrated sensing electrode with unique three-dimensional nanostructure and good electrocatalytic activity. It shows desirable sensing performances for sweat metabolites including tyrosine (Tyr) and uric acid (UA) molecules. The detection limit of Tyr and UA can reach 5.11 µM and 1.37 µM, respectively. Besides, density functional theory calculation deeply reveals that the Fe active sites of FeNCs play an important role in molecule adsorption and electron transference, thus promoting sensing performance. To realize wearable application, a dual-channel hydrogel chip is designed and assembled with FeNCs/LIG. The developed patch is successfully utilized to accurately determination of Tyr and UA in sweat. This work is expected to provide a new non-invasive strategy for evaluating amino acid intake and metabolic level.

The role of olfactory ensheathing cells in the repair of nerve injury.

Cell transplantation has brought about a breakthrough in the treatment of nerve injuries, and the efficacy of cell transplantation compared to drug and surgical therapies is very exciting. In terms of transplantation targets, the classic cells include neural stem cells (NSCs) and Schwann cells, while a class of cells that can exist and renew throughout the life of the nervous system - olfactory ensheathing cells (OECs) - has recently been discovered in the olfactory system. OECs not only encircle the olfactory nerves but also act as macrophages and play an innate immune role. OECs can also undergo reprogramming to transform into neurons and survive and mature after transplantation. Currently, many studies have confirmed the repairing effect of OECs after transplantation into injured nerves, and safe and effective results have been obtained in clinical trials. However, the specific repair mechanism of OECs among them is not quite clear. For this purpose, we focus here on the repair mechanisms of OECs, which are summarized as follows: neuroprotection, secretion of bioactive factors, limitation of inflammation and immune regulation, promotion of myelin and axonal regeneration, and promotion of vascular proliferation. In addition, integrating the aspects of harvesting, purification, and prognosis, we found that OECs may be more suitable for transplantation than NSCs and Schwann cells, but this does not completely discard the value of these classical cells. Overall, OECs are considered to be one of the most promising transplantation targets for the treatment of nerve injury disorders.

Amplification-free microRNA profiling with femtomolar sensitivity on a plasmonic enhanced fluorescence nano-chip.

MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules involved in the regulation of gene expression, thus considered as promising biomarkers for cancer, cardiovascular diseases, neurodegenerative diseases, etc. However, quantitative analysis of miRNAs faces challenges owing to their high homology, small size & ultra-low abundance, and disease occurrence is often related to abnormal expression of multiple miRNAs where method for parallel miRNAs analysis is required. In this work, multiplexed analysis of miRNAs was established on a plasmonic nano-chip capable of fluorescence enhancement in the near-infrared region. Combined with polyadenylation at the hydroxyl terminate of target miRNA to afford abundant sites for fluorophore labeling, our assay achieved amplification-free detection of miRNAs from nM to fM with the limit of detection down to ca. 5 fM. A miRNA panel was constructed to detect 10 miRNAs differentially expressed in MCF-7 and A549 cell lines and validated with qRT-PCR, demonstrating the practical application of this method. This scalable platform can be customized for different miRNA panels, facilitating multiple miRNA profiling for various diseases.

Ion channel P2X7 receptor in the progression of cancer.

P2X7 receptor (P2X7) is a non-selective and ATP-sensitive ligand-gated cation channel. Studies have confirmed that it is expressed in a variety of cells and correlates with their function, frequently in immune cells and tumor cells. We found increased expression of this receptor in many tumor cells, and it has a role in tumor survival and progression. In immune cells, upregulation of the receptor has a double effect on tumor suppression as well as tumor promotion. This review describes the structure of P2X7 and its role in the tumor microenvironment and presents possible mechanisms of P2X7 in tumor invasion and metastasis. Understanding the potential of P2X7 for tumor treatment, we also present several therapeutic agents targeting P2X7 and their mechanisms of action. In conclusion, the study of P2X7 is an important guideline for the use of clinical tumor therapy and may be able to provide a new idea for tumor treatment, but considering the complexity of the biological effects of P2X7, the drugs should be used with caution in clinical practice.

Metabolomics Combined with Transcriptomics Analysis Revealed the Amino Acids, Phenolic Acids, and Flavonol Derivatives Biosynthesis Network in Developing Rosa roxburghii Fruit.

Rosa roxburghii Tratt. is a specific fruit with high nutritional value and antioxidative activities. However, the key metabolites and their biosynthesis are still unknown. Herein, a main cultivated variety, 'Guinong 5' (Rr5), was chosen to analyze the metabolomics of the three developmental stages of R. roxburghii fruit by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 533 metabolites were identified, of which 339 were significantly altered. Total phenols, flavonoids, and amino acids were significantly correlated to at least one in vitro antioxidant activity. The conjoint Kyoto Encyclopedia of Genes and Genomes (KEGG) co-enrichment analysis of metabolome and transcriptome was focused on amino acid, phenylpropanoid, and flavonoid biosynthesis pathways. The amino acid, phenolic acid, and flavonol biosynthesis networks were constructed with 32 structural genes, 48 RrMYBs, and 23 metabolites. Of these, six RrMYBs correlated to 9-15 metabolites in the network were selected to detect the gene expression in six different R. roxburghii genotypes fruits. Subsequently, 21 key metabolites were identified in the in vitro antioxidant activities in the fruits at various developmental stages or in fruits of different R. roxburghii genotypes. We found that four key RrMYBs were related to the significantly varied amino acids, phenolic acids, and flavonol derivatives in the network during fruit development and the key metabolites in the in vitro antioxidative activities in the fruits of six R. roxburghii genotypes. This finding provided novel insights into the flavonoid, polyphenol, and amino acid synthesis in R. roxburghii.

A nano-magnetic size selective cfDNA extraction platform for liquid biopsy with enhanced precision.

As an emerging biomarker, cell-free DNA (cfDNA) carries crucial genetic information for the diagnosis of hereditary disease and cancer. However, test accuracy was severely compromised by the low abundance of cell-free DNA in peripheral blood, frequently diluted by genomic DNA released from white blood cells, resulting in sample rejection, test inaccuracy, and restricted clinical utility. Herein we report a novel strategy for the efficient recovery of cfDNA with significant removal of genomic DNA contamination during the cfDNA extraction process, based on a nano-magnetic size selective cfDNA extraction platform. With this platform, over 90% cfDNA recovery rate was achieved with minimal genomic DNA contamination. For non-invasive prenatal testing, an increase of fetal fraction from 10.10% to 29.94% medially was observed in 11 maternal plasma samples, with two false-negative samples identified by the proposed workflow. Enrichment of cfDNA in plasma sample of cancer patient demonstrated âˆ¼ 100% increase of circulating tumor DNA (ctDNA) percentage by panel sequencing of specific mutation sites. The approach is simple, automatable and cost-efficient, can improve liquid biopsy precision and reduce sequencing depth through significant enrichment of target abundance. The nano-magnetic platform demonstrated its potential application in liquid biopsy, since it exhibited numerous advantages in avoiding false negative results, reducing sequencing cost, improving data quality, and rescuing contaminated samples.

Gene expression profiling in Rosa roxburghii fruit and overexpressing RrGGP2 in tobacco and tomato indicates the key control point of AsA biosynthesis.

Rosa roxburghii Tratt. is an important commercial horticultural crop endemic to China, which is recognized for its extremely high content of L-ascorbic acid (AsA). To understand the mechanisms underlying AsA overproduction in fruit of R. roxburghii, content levels, accumulation rate, and the expression of genes putatively in the biosynthesis of AsA during fruit development have been characterized. The content of AsA increased with fruit weight during development, and AsA accumulation rate was found to be highest between 60 and 90 days after anthesis (DAA), with approximately 60% of the total amount being accumulated during this period. In vitro incubating analysis of 70DAA fruit flesh tissues confirmed that AsA was synthesized mainly via the L-galactose pathway although L-Gulono-1, 4-lactone was also an effective precursor elevating AsA biosynthesis. Furthermore, in transcript level, AsA content was significantly associated with GDP-L-galactose phosphorylase (RrGGP2) gene expression. Virus-induced RrGGP2 silencing reduced the AsA content in R. roxburghii fruit by 28.9%. Overexpressing RrGGP2 increased AsA content by 8-12-fold in tobacco leaves and 2.33-3.11-fold in tomato fruit, respectively, and it showed enhanced resistance to oxidative stress caused by paraquat in transformed tobacco. These results further justified the importance of RrGGP2 as a major control step to AsA biosynthesis in R. roxburghii fruit.

Distinction of chiral penicillamine using metal-ion coupled cyclodextrin complex as chiral selector by trapped ion mobility-mass spectrometry and a structure investigation of the complexes.

Penicillamine (Pen) is a common chiral drug that is obtained from penicillin. Between the two enantiomers of Pen, only D-Pen can be used to treat cystinuria and rheumatoid arthritis while L-Pen is toxic. Therefore, it requires great efforts for the research of the rigorous analysis and distinction of the two enantiomers. The non-covalent combination of chiral molecules and chiral selectors (CSs) has been proved as a unique strategy for chiral distinction by ion mobility spectrometry in coupling with -mss spectrometry (IM-MS). Here, we developed a simple method to distinguish D, L-Pen by using special CSs for IM-MS separation. The CSs utilized here include cyclodextrins (CD) and linear chain oligosaccharides plus metal ions. We found that non-covalent complexes [Pen+ß-CD + Li]+ could be easily formed by electrospray ionization of the mixture of the solution, and the chirality of Pen could be effectively recognized by measuring their mobilities due to the different collision cross collision sections of [D-Pen+ß-CD + Li]+ and [L-Pen+ß-CD + Li]+. A detailed analysis of [Pen+ß-CD + Li]+ was then conducted by the optical rotation measurements and NMR experiments to reveal their structural differences. Furthermore, DFT calculation showed the differences of molecular conformation between the complexes. The results provide a new powerful method for fast analysis and recognition of chirality of Pen compounds by IM-MS.

miR-4721, Induced by EBV-miR-BART22, Targets GSK3ß to Enhance the Tumorigenic Capacity of NPC through the WNT/ß-catenin Pathway.

Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo. Mechanism analysis indicated that miR-4721 directly targetes GSK3ß and reduces its expression, which therefore elevates ß-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3ß are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3ß, which thus activates the WNT/ß-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future.

Silencing MYH9 blocks HBx-induced GSK3ß ubiquitination and degradation to inhibit tumor stemness in hepatocellular carcinoma.

MYH9 has dual functions in tumors. However, its role in inducing tumor stemness in hepatocellular carcinoma (HCC) is not yet determined. Here, we found that MYH9 is an effective promoter of tumor stemness that facilitates hepatocellular carcinoma pathogenesis. Importantly, targeting MYH9 remarkably improved the survival of hepatocellular carcinoma-bearing mice and promoted sorafenib sensitivity of hepatocellular carcinoma cells in vivo. Mechanistic analysis suggested that MYH9 interacted with GSK3ß and reduced its protein expression by ubiquitin-mediated degradation, which therefore dysregulated the ß-catenin destruction complex and induced the downstream tumor stemness phenotype, epithelial-mesenchymal transition, and c-Jun signaling in HCC. C-Jun transcriptionally stimulated MYH9 expression and formed an MYH9/GSK3ß/ß-catenin/c-Jun feedback loop. X protein is a hepatitis B virus (HBV)-encoded key oncogenic protein that promotes HCC pathogenesis. Interestingly, we observed that HBV X protein (HBX) interacted with MYH9 and induced its expression by modulating GSK3ß/ß-catenin/c-Jun signaling. Targeting MYH9 blocked HBX-induced GSK3ß ubiquitination to activate the ß-catenin destruction complex and suppressed cancer stemness and EMT. Based on TCGA database analysis, MYH9 was found to be elevated and conferred poor prognosis for hepatocellular carcinoma patients. In clinical samples, high MYH9 expression levels predicted poor prognosis of hepatocellular carcinoma patients. These findings identify the suppression of MYH9 as an alternative approach for the effective eradication of CSC properties to inhibit cancer migration, invasion, growth, and sorafenib resistance in HCC patients. Our study demonstrated that MYH9 is a crucial therapeutic target in HCC.