Hypoxia stabilizes SETDB1 to maintain genome stability.

Von Hippel-Lindau (VHL) is a tumor suppressor that functions as the substrate recognition subunit of the CRL2VHL E3 complex. While substrates of VHL have been identified, its tumor suppressive role remains to be fully understood. For further determination of VHL substrates, we analyzed the physical interactome of VHL and identified the histone H3K9 methyltransferase SETBD1 as a novel target. SETDB1 undergoes oxygen-dependent hydroxylation by prolyl hydroxylase domain proteins and the CRL2VHL complex recognizes hydroxylated SETDB1 for ubiquitin-mediated degradation. Under hypoxic conditions, SETDB1 accumulates by escaping CRL2VHL activity. Loss of SETDB1 in hypoxia compared with that in normoxia escalates the production of transposable element-derived double-stranded RNAs, thereby hyperactivating the immune-inflammatory response. In addition, strong derepression of TEs in hypoxic cells lacking SETDB1 triggers DNA damage-induced death. Our collective results support a molecular mechanism of oxygen-dependent SETDB1 degradation by the CRL2VHL E3 complex and reveal a role of SETDB1 in genome stability under hypoxia.

Anti-Inflammatory Flavonoids from Agrimonia pilosa Ledeb: Focusing on Activity-Guided Isolation.

To elucidate the anti-inflammatory properties and constituents of Agrimonia pilosa Ledeb. (A. pilosa), a comprehensive investigation was conducted employing activity-guided isolation. The anti-inflammatory effects were evaluated through an in vitro nitric oxide (NO) assay on lipopolysaccharide (LPS)-treated RAW 264.7 macrophage cells. Seven bio-active compounds with anti-inflammatory properties were successfully isolated from the butanol fraction and identified as follows: quercetin-7-O-ß-d-rhamnoside (1), apigenin-7-O-ß-d-glucopyranoside (2), kaempferol-7-O-ß-d-glucopyranoside (3), quercetin (4), kaempferol (5), apigenin (6), and apigenin-7-O-ß-d-glucuronide-6″-butylester (7). All isolated compounds showed strong NO inhibitory activity with IC50 values ranging from 1.4 to 31 µM. Compound 6 demonstrated the most potent NO inhibition. Compound 7, a rare flavonoid, was discerned as a novel anti-inflammatory agent, ascertained through its inaugural demonstration of nitric oxide inhibition. Subsequently, a comprehensive structure-activity relationship (SAR) analysis was conducted employing eight flavonoids derived from A. pilosa. The outcomes elucidated that flavones exhibit superior NO inhibitory effects compared to flavonols, and the aglycone form manifests greater potency in NO inhibition than the glycone counterpart. These results highlight A. pilosa as a promising source of effective anti-inflammatory agents and indicate its potential as a health-beneficial dietary supplement and therapeutic material.

Widening Social Inequalities in Cancer Mortality of Children Under 5 Years in Korea.

BACKGROUND: To investigate the effect of parental social class on cancer mortality in children under 5 in Korea, two birth cohorts were constructed by linking national birth data to under-5 death data from the Statistics Korea for 1995-1999 (3,323,613 births) and 2010-2014 (2,297,876 births). METHODS: The Cox proportional hazards model adjusted for covariates was used in this study. RESULTS: Social inequalities of under-5 cancer mortality risk in paternal education and paternal employment status were greater in 2010-2014 than in 1995-1999. The gap of hazard ratio (HR) of under-5 cancer mortality between lower (high school or below) and higher (university or higher) paternal education increased from 1.23 (95% confidence interval, 1.041.46) in 1995-1999 to 1.45 (1.11-1.97) in 2010-2014; the gap of HR between parents engaged in manual work and non-manual work increased from 1.32 (1.12-1.56) in 1995-1999 to 1.45 (1.12-1.89) in 2010-2014 for fathers, and from 1.18 (0.7-1.98) to 1.69 (1.03-2.79) for mothers. When the parental social class was lower, the risk of under-5 cancer mortality was higher in not only adverse but normal births. CONCLUSION: Social inequalities must be addressed to reduce the disparity in cancer mortality of children under 5 years old.

Inhibition of Melanogenesis by Essential Oils from the Citrus Cultivars Peels.

Citrus is one of the most popular and widely grown fruit crops in the world. However, the bioactivity of only certain species of citrus cultivars is studied. In this study, the effects of essential oils from 21 citrus cultivars on melanogenesis were investigated in an effort to identify active anti-melanogenesis constituents. The essential oils from the peels of 21 citrus cultivars obtained by hydro-distillation were analyzed using gas chromatography-mass spectrometry. Mouse melanoma B16BL6 cells were used in all assays conducted in this study. The tyrosinase activity and melanin content were determined using the lysate of α-Melanocyte-stimulated B16BL6 cells. In addition, the melanogenic gene expression was determined by quantitative reverse transcription-polymerase chain reaction. Overall, the essential oils of (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulata provided the best bioactivity and comprised five distinct constituents compared to other essential oils such as limonene, farnesene, ß-elemene, terpinen-4-ol, and sabinene. The anti-melanogenesis activities of the five individual compounds were evaluated. Among the five essential oils, ß-elemene, farnesene, and limonene showed dominating properties. The experimental results indicated that (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulara are potential candidates with anti-melanogenesis activity for use as cosmetics and pharmaceutical agents against skin hyperpigmentation.

Estimates of particulate matter inhalation doses during three-dimensional printing: How many particles can penetrate into our body?

Harmful emissions including particulates, volatile organic compounds, and aldehydes are generated during three-dimensional (3D) printing. Ultrafine particles are particularly important due to their ability to penetrate deep into the lung. We modeled inhalation exposure by particle size during 3D printing. A total of six thermoplastic filaments were used for printing under manufacturer's recommended conditions, and particle emissions in the size range between 10 nm and 10 µm were measured. The inhalation exposure dose including inhaled and deposited doses was estimated using a mathematical model. For all materials, the number of particles between 10 nm and 1 µm accounted for a large proportion among the released particles, with nano-sized particles being the dominant size. More than 1.3 × 109 nano-sized particles/kgbw/g (95.3 ± 104.0 ng/kgbw/g) could be inhaled, and a considerable amount was deposited in respiratory regions. The total deposited dose in terms of particle number was 3.1 × 108 particles/kgbw/g (63.6% of the total inhaled dose), and most (41.3%) were deposited in the alveolar region. The total mass of particles deposited was 19.8 ± 16.6 ng/kgbw/g, with 10.1% of the total mass deposited in the alveolar region. Given our findings, the inhalation exposure level is mainly determined by printing conditions, particularly the filament type and manufacturer-recommended extruder temperature.

LAD1 expression is associated with the metastatic potential of colorectal cancer cells.

BACKGROUND: Anchoring filament protein ladinin-1 (LAD1) was related to the aggressive progression of breast, lung, laryngeal and thyroid cancers. However, the association of LAD1 with colorectal cancer remained unknown. Here, to determine the relationship of LAD1 with colorectal cancer progression, we explored the effect of LAD1 loss on the malignant features of colorectal cancer cells. METHODS: We constructed LAD1-depleted cell lines and examined the effect of LAD1 deficiency on the phenotypic and molecular features of colorectal cancer cells in vitro. The function of LAD1 in metastasis in vivo was examined by establishing a spleen-to-liver metastasis mouse model. LAD1 protein expression in colorectal cancer patient specimens was assessed by immunohistochemistry of tumor microarrays. RESULTS: We found that LAD1 was abundant in most colorectal cancer cells. In addition, high expression of LAD1 significantly correlated with poor patient outcome. LAD1 depletion inhibited the migration and invasion of two different colorectal cancer cell lines, SW620 and Caco-2, without affecting their proliferation. In addition, LAD1 loss led to defects in liver metastasis of SW620 cells in the mouse model. Immunohistochemistry of colorectal cancer tissues revealed LAD1 enrichment in metastatic tissues compared to that in primary tumor and normal tissues. CONCLUSION: These results suggest that LAD1 expression is associated with the metastatic progression of colorectal cancer by promoting the migration and invasion of cancer cells.

An Easy-to-Use Machine Learning Model to Predict the Prognosis of Patients With COVID-19: Retrospective Cohort Study.

BACKGROUND: Prioritizing patients in need of intensive care is necessary to reduce the mortality rate during the COVID-19 pandemic. Although several scoring methods have been introduced, many require laboratory or radiographic findings that are not always easily available. OBJECTIVE: The purpose of this study was to develop a machine learning model that predicts the need for intensive care for patients with COVID-19 using easily obtainable characteristics-baseline demographics, comorbidities, and symptoms. METHODS: A retrospective study was performed using a nationwide cohort in South Korea. Patients admitted to 100 hospitals from January 25, 2020, to June 3, 2020, were included. Patient information was collected retrospectively by the attending physicians in each hospital and uploaded to an online case report form. Variables that could be easily provided were extracted. The variables were age, sex, smoking history, body temperature, comorbidities, activities of daily living, and symptoms. The primary outcome was the need for intensive care, defined as admission to the intensive care unit, use of extracorporeal life support, mechanical ventilation, vasopressors, or death within 30 days of hospitalization. Patients admitted until March 20, 2020, were included in the derivation group to develop prediction models using an automated machine learning technique. The models were externally validated in patients admitted after March 21, 2020. The machine learning model with the best discrimination performance was selected and compared against the CURB-65 (confusion, urea, respiratory rate, blood pressure, and 65 years of age or older) score using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 4787 patients were included in the analysis, of which 3294 were assigned to the derivation group and 1493 to the validation group. Among the 4787 patients, 460 (9.6%) patients needed intensive care. Of the 55 machine learning models developed, the XGBoost model revealed the highest discrimination performance. The AUC of the XGBoost model was 0.897 (95% CI 0.877-0.917) for the derivation group and 0.885 (95% CI 0.855-0.915) for the validation group. Both the AUCs were superior to those of CURB-65, which were 0.836 (95% CI 0.825-0.847) and 0.843 (95% CI 0.829-0.857), respectively. CONCLUSIONS: We developed a machine learning model comprising simple patient-provided characteristics, which can efficiently predict the need for intensive care among patients with COVID-19.

Integrated Analysis of Tissue-Specific Promoter Methylation and Gene Expression Profile in Complex Diseases.

This study investigated whether the promoter region of DNA methylation positively or negatively regulates tissue-specific genes (TSGs) and if it correlates with disease pathophysiology. We assessed tissue specificity metrics in five human tissues, using sequencing-based approaches, including 52 whole genome bisulfite sequencing (WGBS), 52 RNA-seq, and 144 chromatin immunoprecipitation sequencing (ChIP-seq) data. A correlation analysis was performed between the gene expression and DNA methylation levels of the TSG promoter region. The TSG enrichment analyses were conducted in the gene-disease association network (DisGeNET). The epigenomic association analyses of CpGs in enriched TSG promoters were performed using 1986 Infinium MethylationEPIC array data. A correlation analysis showed significant associations between the promoter methylation and 449 TSGs' expression. A disease enrichment analysis showed that diabetes- and obesity-related diseases were high-ranked. In an epigenomic association analysis based on obesity, 62 CpGs showed statistical significance. Among them, three obesity-related CpGs were newly identified and replicated with statistical significance in independent data. In particular, a CpG (cg17075888 of PDK4), considered as potential therapeutic targets, were associated with complex diseases, including obesity and type 2 diabetes. The methylation changes in a substantial number of the TSG promoters showed a significant association with metabolic diseases. Collectively, our findings provided strong evidence of the relationship between tissue-specific patterns of epigenetic changes and metabolic diseases.

Impact of social capital on depression trajectories of older women in Korea.

OBJECTIVES: This study examines the impact of social capital on depressive symptoms trajectories among Korean women aged 65 years or older. It also examines the difference in depressive symptoms and social capital by economic status (poverty group, non-poverty group) among community-dwelling older women in Korea. METHOD: This study used 2435 older women of the Korean Welfare Panel Study from 2006 (wave 1) to 2013 (wave 8) data using latent growth modeling. Social capital variables were cognitive (interpersonal trust, reciprocity) and structural (the size of family, the number of friends or neighbors, participation in leisure and volunteer activities). RESULTS: The results showed both intra- and inter-individual variability in depressive symptoms over time. Interpersonal trust and reciprocity as cognitive social capital had an effect on the change of depressive symptoms in intercept and slope. The size of family, participation in leisure activities among structural social capital were associated with lower levels of depressive symptoms in intercept and slope. CONCLUSION: The results of this study suggest some practical implications for depression intervention and prevention and further research on late-life depression.

MicroRNA-155 regulates the Th17 immune response by targeting Ets-1 in Behçet's disease.

OBJECTIVES: The goal of this study was to investigate whether microRNA-155 might be a potential therapeutic target for Behçet's disease (BD). METHODS: Expression levels of miR-155 were quantified using TaqMan microRNA assays in peripheral blood mononuclear cells and in isolated CD4+ T cells from BD patients and healthy controls. To identify targets of miR-155, luciferase reporter assays and western blotting were performed. The effect of miR-155 on Th17 polarisation was analysed in patients with active BD by using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The expression of miR-155 and IL-17 was significantly increased in CD4+ T cells of patients with active BD. A luciferase reporter assay and western blot showed that Ets-1 expression was reduced by miR-155 mimics. Furthermore, the expression of Ets-1 was significantly decreased in patients with active BD compared to healthy controls. More importantly, repression of miR-155 in CD4+ T cells from active BD patients increased Ets-1 expression and reduced the number of IL- 17-expressing T cells and overall IL-17 production. CONCLUSIONS: MiR-155 regulates the Th17 immune response by targeting Ets-1. Suppression of miR-155 reduced the amount of pathogenic IL-17-expressing T cells and may be a potential therapeutic strategy for BD.

The effects of health on the life satisfaction of poor and nonpoor older women in Korea.

This research examined the relationship between health and life satisfaction in women over 65 years of age in local communities. The World Health Organization's definition of health as physical, mental, and social well-being was used as the foundation for analyzing the effects of health on life satisfaction. The Korean Longitudinal Study of Aging was utilized to analyze data from 2,356 women over 65. Our results showed that significant influential factors included satisfaction in relationship with children, self-rated health, depression, participation in social activities, and number of family members. Our findings suggest how older women's health and life satisfaction can be improved, and give necessary directions for future studies.

Airborne and surface contamination after rotational intraperitoneal pressurized aerosol chemotherapy using cisplatin.

OBJECTIVE: We evaluated the occupational exposure levels of healthcare workers while conducting rotational pressurized intraperitoneal aerosol chemotherapy (RIPAC) using cisplatin in a large animal model. METHODS: We performed RIPAC using cisplatin in 6 female pigs and collected surface and air samples during the procedure. Surface samples were obtained from RIPAC devices and personal protective equipment (PPE) by wiping, and air samples were collected around the operating table. All samples were analyzed by inductively coupled plasma-mass spectrometry to detect platinum. RESULTS: Among all surface samples (n=44), platinum was detected in 41 samples (93.2%) but not in all air samples (n=16). Among samples collected from RIPAC devices (n=23), minimum and maximum cisplatin levels of 0.08 and 235.09 ng/cm² were detected, mainly because of direct aerosol exposure in the abdominal cavity. Among samples collected from healthcare workers' PPE (n=21), 18 samples (85.7%) showed contamination levels below the detection limit, with a maximum of 0.23 ng/cm². There was no significant contamination among samples collected from masks, shoes, or gloves. CONCLUSION: During the RIPAC procedures, there is a potential risk of dermal exposure, as platinum, a surrogate material for cisplatin, was detected at low concentration levels in some surface samples. However, the respiratory exposure risk was not identified, as platinum was not detected in the airborne samples in this study.

Essential oils extracted from nine different plants exhibit differential effects on skin antioxidation and elasticity.

Essential oils derived from plants are major ingredients in the medical and cosmetic industry. Here, we evaluated nine types of plant essential oils to identify potential candidates with antioxidant and elasticity-enhancing properties. Seven essential oils showed at least 10% radical scavenging activity at the highest concentration. Essential oils extracted from Aster glehnii, Cinnamomum cassia, Citrus unshiu, Juniperus chinensis L., and Juniperus chinensis var. sargentii significantly enhanced fibroblast viability, and oils from Cit. unshiu, J. chinensis L., and J. chinensis var. sargentii significantly increased cell proliferation and migration. Expression of extracellular matrix proteins, including collagen 1, collagen 3, and elastin, were upregulated by J. chinensis L. and J. chinensis var. sargentii oil, which also significantly enhanced the contractile activity of skin cells in a three-dimensional gel contraction assay. The results suggest that J. chinensis L. and J. chinensis var. sargentii essential oils may be potential anti-wrinkling and anti-oxidative agents for future consideration of use in the medical and cosmetic industry.

Up-regulation of Th17 and related cytokines in Behçet's disease corresponding to disease activity.

OBJECTIVES: The IL-23/IL-17 pathway is implicated in the development of certain inflammatory diseases. The aim of the present study was to investigate the expression of Th17 and related cytokines according to clinical activity in Behçet's disease (BD). METHODS: Peripheral blood mononuclear cells (PBMCs) from eleven patients with active BD, eleven patients with inactive BD, ten patients with recurrent aphthous ulcers, and ten healthy controls were cultured and stained with the appropriate fluorescent antibodies for analysis by flow cytometry. ELISA assays were utilized to determine the concentrations of IL-17, IFN-γ, IL-23, and IL-12/23p40 in serum and culture supernatants. IL-12p35, IL-12/23p40, and IL-23p19 transcript levels in PBMCs were measured by real-time PCR. RESULTS: Significantly higher frequencies of IL-17 and IFN-γ expressing CD4(+) T cells were observed in patients with active BD compared with control groups. Similarly, levels of IL-17, IL-23, IL-12/23p40, and IFN-γ in serum and supernatants were significantly elevated in patients with BD despite the fact that IL-12p35 and IL-12/23p40 mRNA expression in PBMCs was up-regulated in the inactive BD group. In the same patient, the frequency of IL-17 expressing cells decreased when the BD disease activity was stabilised. CONCLUSIONS: The results of this study suggest that up-regulated IL-17 expression may be associated with clinical activity of BD.

Social inequality in birth outcomes in Korea, 1995-2008.

Social inequality in adverse birth outcomes has been demonstrated in several countries. The present study examined the separate and joint effects of parental education and work in order to investigate the causal pathways of social class effects on adverse birth outcomes in Korea. The occurrence of low birth weight, preterm births, and intrauterine growth retardation was examined among 7,766,065 births in Korea from 1995 to 2008. The effect of social inequality, as represented by parental education and work, was examined against adverse birth outcomes using multivariate logistic regression after controlling for other covariates. Parental education had the most significant and greatest effect on all three adverse outcomes, followed by parental work and employment, which had lesser effects. For adverse birth outcomes, the gap between educational levels increased steadily in Korea from 1995 to 2008. Throughout the analysis, the effect of maternal manual work on adverse birth outcomes was apparent in the study results. Given this evidence of social inequality in education and employment, social interventions should aim at more in-depth and distal determinants of health.

A genetic link between cold responses and flowering time through FVE in Arabidopsis thaliana.

Cold induces expression of a number of genes that encode proteins that enhance tolerance to freezing temperatures in plants. A cis-acting element responsive to cold and drought, the C-repeat/dehydration-responsive element (C/DRE), was identified in the Arabidopsis thaliana stress-inducible genes RD29A and COR15a and found in other cold-inducible genes in various plants. C/DRE-binding factor/DRE-binding protein (CBF/DREB) is an essential component of the cold-acclimation response, but the signaling pathways and networks are mostly unknown. Here we used targeted genetic approach to isolate A. thaliana mutants with altered cold-responsive gene expression (acg) and identify ACG1 as a negative regulator of the CBF/DREB pathway. acg1 flowered late and had elevated expression of FLOWERING LOCUS C (FLC), a repressor of flowering encoding a MADS-box protein. We showed that acg1 is a null allele of the autonomous pathway gene FVE. FVE encodes a homolog of the mammalian retinoblastoma-associated protein, a component of a histone deacetylase (HDAC) complex involved in transcriptional repression. We also showed that plants sense intermittent cold stress through FVE and delay flowering with increasing expression of FLC. Dual roles of FVE in regulating the flowering time and the cold response may have an evolutionary advantage for plants by increasing their survival rates.

A multilevel perspective on gender differences in the relationship between poverty status and depression among older adults in the United States.

Despite a large body of literature on depression, previous studies have focused on either intra- or interpersonal factors but not multilevel influences, which potentially could buffer depression in late life. The intent of this study was to identify whether the impact of poverty might be moderated by multilevel factors such as sense of control, social support, and neighborhood environment. The results showed that the elderly poor, especially older women, were more likely to be depressed. Support from friends significantly moderated the association between depression and poverty among older women. Implications for critical feminist gerontology and for practice are discussed.

Development of Pinaceae and Cupressaceae Essential Oils from Forest Waste in South Korea.

The growing awareness of environmental issues has garnered increasing interest in the use of waste material in a wide variety of applications. From this viewpoint, developing essential oils from forest waste can bring new cost opportunities for the effective and sustainable management of unused forestry biomass. However, better knowledge of the production, chemical constituents, and application of essential oils is necessary. Among the species considered to be of interest from the point of view of their essential oils and forest biomass, Pinaceae and Cupressaceae were selected in this study as potential candidates for commercial essential oils based on previous studies. This current study focuses on investigating Pinaceae (Larix kaempferi, Pinus densiflora, and Pinus koraiensis) and Cupressaceae (Chamaecyparis obtusa and Chamaecyparis pisifera) essential oils extracted from various parts from the perspective of their bioactive compounds and potential applications. This is followed by an overview of the essential oils industry in South Korea, with particular attention being paid to utilising unused forest biomass. Therefore, this is a comprehensive review suggesting that Pinaceae and Cupressaceae essential oils extracted from various parts of forest waste could be utilised in various industries, adding value to the aspect of sustainable industry. Furthermore, our study contributes towards capturing the value of forest resources through the utilisation of native essential oils in South Korea.

Anti-Inflammatory Effects of Essential Oils from the Peels of Citrus Cultivars.

Citrus cultivars have remarkable health benefits, but only the anti-inflammatory activities of the major varieties have been studied. This study investigated the anti-inflammatory effects of various citrus cultivars and their active anti-inflammatory components. The essential oils of 21 citrus peels were extracted via hydrodistillation using a Clevenger-type apparatus, and the chemical compositions of the essential oils were analyzed. D-Limonene was the most abundant constituent. To evaluate the anti-inflammatory effects of the citrus cultivars, the gene expression levels of an inflammatory mediator and proinflammatory cytokines were investigated. Among the 21 essential oils, those extracted from C. japonica and C. maxima exhibited superior anti-inflammatory activities, being able to inhibit the expression of the inflammatory mediators and proinflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The essential oils of C. japonica and C. maxima were distinguished into seven distinct constituents, α-pinene, myrcene, D-limonene, ß-ocimene, linalool, linalool oxide, and α-terpineol, compared with other essential oils. The anti-inflammatory activities of the seven single compounds significantly inhibited the levels of inflammation-related factors. In particular, α-terpineol exhibited a superior anti-inflammatory effect. This study showed that the essential oils from C. japonica and C. maxima exhibit high anti-inflammatory activity. In addition, α-terpineol is an active anti-inflammatory compound that contributes to inflammatory responses.

CDK9 inhibitors downregulate DKK1 expression to suppress the metastatic potential of HCC cells.

BACKGROUND: Elevated expression of Dickkopf-1 (DKK1) is frequently observed in hepatocellular carcinoma (HCC) patients with poor clinical outcomes. Several reports indicating the functional involvement of DKK1 in HCC progression have suggested DKK1 as a promising therapeutic target for HCC. OBJECTIVE: In this study, to develop an efficient way to target DKK1, we assessed the effect of CDK9 inhibitors on DKK1 expression linked to metastatic movement of HCC. METHODS: The expression of DKK1 in CDK9 inhibitor-treated HCC cells was measured by western blot, ELISA and quantitative real-time reverse transcription PCR. Wound healing assay, migration assay, invasion assay and western blot were examined to evaluate the functional role of DKK1 in CDK9 inhibitors-treated HCC. RESULTS: Inactivation of CDK9 either by a catalytic inhibitor being clinically evaluated or by a specific CDK9 protein degrader largely downregulated DKK1 expression at the transcript and protein levels. In addition, CDK9 inhibitors suppressed the migration and invasion of HCC cells. We observed that ectopic high expression of DKK1 at least partially reversed the defects in metastatic movement of HCC cells mediated by CDK9 inhibitors. We further discovered that the DKK1-nuclear ß-catenin axis associated with the metastatic potential of HCC cells was impaired by CDK9 inhibitors. CONCLUSION: Taken together, our findings suggest that CDK9 inhibitors are potent tools to target DKK1, which can suppress the metastatic progression of HCC.