LncRNA NBAT-1 inhibits the progression of hepatocellular carcinoma by interacting with CYLD

Purpose: To illustrate the biological influences of long non-coding RNA (lncRNA) NBAT-1 (neuroblastoma associated transcript 1) on HCC progression and the molecular mechanism of action. Methods: NBAT-1 levels in HCC tissues and cell lines were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between NBAT-1 and prognosis in HCC was analyzed. After knockdown of NBAT-1 in HepG2 and Hep3B cells, proliferative and migratory changes were assessed by cell counting kit-8 (CCK-8) and Transwell assay, respectively. The interaction between NBAT-1 and CYLD was confirmed by subcellular fraction determination and RNA binding protein immunoprecipitation (RIP). Rescue experiments were conducted to verify the involvement of CYLD in HCC cell functions regulated by NBAT-1. Results: NBAT-1 was downregulated in HCC tissues. Its level was much lower in metastatic or advanced stage HCC patients (p < 0.05), showing a certain prognostic potential. Knockdown of NBAT-1 stimulated proliferative and migratory potentials in HepG2 and Hep3B cells. NBAT-1 was mainly distributed in the cell cytoplasm. The mRNA and protein levels of CYLD were downregulated in HCC cells by NBAT-1 knockdown, displaying a positive interaction. CYLD was involved in the regulatory effect of NBAT-1 on HCC progression. Conclusion: Through a positive interaction with CYLD, NBAT-1 inhibits the malignant progression of HCC. These findings provide a potential approach to the development of targeted therapies for HCC

Dissecting the association between gut microbiota and liver cancer in European and East Asian populations using Mendelian randomization analysis

BackgroundAmple evidence suggests an important role of the gut microbiome in liver cancer, but the causal relationship between gut microbiome and liver cancer is unclear. This study employed Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiome and liver cancer in European and East Asian populations.MethodsWe sourced genetic variants linked to gut microbiota from the MiBioGen consortium meta-analysis, and procured liver cancer genome-wide association study (GWAS) summary data from the FinnGen consortium and Biobank Japan. We employed the inverse variance weighted method for primary statistical analysis, fortified by several sensitivity analyses such as MR-PRESSO, MR-Egger regression, weighted median, weighted mode, and maximum likelihood methods for rigorous results. We also evaluated heterogeneity and horizontal pleiotropy.ResultsThe study examined an extensive set of gut microbiota, including 131 genera, 35 families, 20 orders, 16 classes, and 9 phyla. In Europeans, ten gut microbiota types displayed a suggestive association with liver cancer (p < 0.05). Notably, Oscillospira and Mollicutes RF9 exhibited a statistically significant positive association with liver cancer risk, with odds ratios (OR) of 2.59 (95% CI 1.36–4.95) and 2.03 (95% CI 1.21–3.40), respectively, after adjusting for multiple testing. In East Asians, while six microbial types demonstrated suggestive associations with liver cancer, only Oscillibacter displayed a statistically significant positive association (OR = 1.56, 95% CI 1.11–2.19) with an FDR < 0.05. Sensitivity analyses reinforced these findings despite variations in p-values.ConclusionThis study provides evidence for a causal relationship between specific gut microbiota and liver cancer, enhancing the understanding of the role of the gut microbiome in liver cancer and may offer new avenues for preventive and therapeutic strategies

Nectin2 influences cell apoptosis by regulating ANXA2 expression in neuroblastoma

Neuroblastoma (NB) is a pediatric cancer of the peripheral sympathetic nervous system and represents the most frequent solid malignancy in infants. Nectin2 belongs to the immunoglobulin superfamily and has been shown to play a role in tumorigenesis. In the current study, we demonstrate that serum Nectin2 level is increased in NB patients compared with that in healthy controls and Nectin2 level is correlated with neuroblastoma international neuroblastoma staging system (INSS) classification. There is a positive correlation between Nectin2 level and shorter overall survival in NB patients. Knockdown of Nectin2 reduces the migration of SH-SY5Y and SK-N-BE2 cells and induces their apoptosis and cell cycle arrest. RNA-seq analysis demonstrates that Nectin2 knockdown affects the expressions of 258 genes, including 240 that are upregulated and 18 that are downregulated compared with negative controls. qRT-PCR and western blot analysis confirm that ANXA2 expression is decreased in Nectin2-knockdown SH-SY5Y cells, consistent with the RNA-seq results. ANXA2 overexpression rescues the percentage of apoptotic NB cells induced by Nectin2 knockdown and compensates for the impact of Nectin2 knockdown on cleaved caspase3 and bax expressions. In addition, western blot analysis results show that ANXA2 overexpression rescues the effect of Nectin2 knockdown on MMP2 and MMP9 expressions. The current data highlight the importance of Nectin2 in NB progression and the potential of Nectin2 as a novel candidate target for gene therapy

Hepatoblastoma with neonatal necrotizing enterocolitis: Two case reports

Abstract We report two children with hepatoblastoma (HB) with a history of neonatal necrotizing enterocolitis (NEC). Case 1 was diagnosed with HB at 5 months of age. Liver enlargement was found during the NEC operation at 3 months of age and then was clinically diagnosed by imaging. After six chemotherapy courses, a partial hepatectomy was performed. Three months after ceasing the chemotherapy, a chest computed tomography scan suggested that distant metastasis of the tumor should be considered, and the lesion was removed. However, 9 months after the operation, alpha‐fetoprotein concentrations were increased, and abdominal imaging showed a recurrence of the tumor in situ, resulting in a hepatectomy. Case 2 was diagnosed with NEC shortly after birth and underwent an intestinal resection and anastomosis 1 month later. He was diagnosed with HB at 3 years of age. Hepatectomy was performed after five courses of chemotherapy. Chemotherapy was stopped after 10 courses, and alpha‐fetoprotein concentrations were normal. At present, both children have survived and are in a healthy condition. Physicians should be aware of the possibility of HB and a history of NEC in children. Premature birth and low birth weight are common factors leading to the pathogenesis of HB and NEC. The association between these two diseases requires further study

BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma

Abstract Background Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB. Methods The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels. Results Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression. Conclusions A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It’s also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways

Association between mental disorders and subsequent adult onset asthma

BACKGROUND AND OBJECTIVES: Associations between asthma and anxiety and mood disorders are well established, but little is known about their temporal sequence. We examined associations between a wide range of DSM-IV mental disorders with adult onset of asthma and whether observed associations remain after mental comorbidity adjustments. METHODS: During face-to-face household surveys in community-dwelling adults (n = 52,095) of 19 countries, the WHO Composite International Diagnostic Interview retrospectively assessed lifetime prevalence and age at onset of 16 DSM-IV mental disorders. Asthma was assessed by self-report of physician's diagnosis together with age of onset. Survival analyses estimated associations between first onset of mental disorders and subsequent adult onset asthma, without and with comorbidity adjustment. RESULTS: 1860 adult onset (21 years+) asthma cases were identified, representing a total of 2,096,486 person-years of follow up. After adjustment for comorbid mental disorders several mental disorders were associated with subsequent adult asthma onset: bipolar (OR = 1.8; 95%CI 1.3-2.5), panic (OR = 1.4; 95%CI 1.0-2.0), generalized anxiety (OR = 1.3; 95%CI 1.1-1.7), specific phobia (OR = 1.3; 95%CI 1.1-1.6); post-traumatic stress (OR = 1.5; 95%CI 1.1-1.9); binge eating (OR = 1.8; 95%CI 1.2-2.9) and alcohol abuse (OR = 1.5; 95%CI 1.1-2.0). Mental comorbidity linearly increased the association with adult asthma. The association with subsequent asthma was stronger for mental disorders with an early onset (before age 21). CONCLUSIONS: A wide range of temporally prior mental disorders are significantly associated with subsequent onset of asthma in adulthood. The extent to which asthma can be avoided or improved among those with early mental disorders deserves study.The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the National Institute of Mental Health (NIMH; R01 MH070884); the John D. and Catherine T. MacArthur Foundation; the Pfizer Foundation; the US Public Health Service (R13-MH066849, R01-MH069864, R01 DA016558); the Fogarty International Center (FIRCA R03-TW006481).The European surveys were funded by the European Commission (Contracts QLG5-1999-01042, SANCO 2004123, EAHC 20081308); Spain (FIS 00/0028); Ministerio de Ciencia y Tecnología, Spain (SAF 2000-158-CE); Departament de Salut, Generalitat de Catalunya, Spain; Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP).The World Mental Health Japan (WMHJ) Survey was supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The Mexican National Comorbidity Survey (MNCS) was supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H). The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health(NIMH; U01-MH60220) and the Robert Wood Johnson Foundation (RWJF; Grant 044708