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Background: This study aimed to probe and verify aberrantly methylated and expressed genes in hepatoblastoma and to analyze their interactions with tumor immune microenvironment.Methods: Aberrantly methylated and expressed genes were obtained by comprehensively analyzing gene expression and DNA methylation profiles from GSE81928, GSE75271 and GSE78732 datasets. Their biological functions were predicted by the STRING and Metascape databases. CIBERSORT was utilized for inferring the compositions of tumor-infiltrating immune cells (TIICs) in each sample. Correlation between hub genes and immune cells was then analyzed. Hub genes were validated in hepatoblastoma tissues via western blot or immunohistochemistry. After transfection with sh-NOTUM, migration and invasion of HuH-6 and HepG2 cells were investigated. The nude mouse tumorigenesis model was constructed.Results: Totally, 83 aberrantly methylated and expressed genes were determined in hepatoblastoma, which were mainly involved in metabolic and cancer-related pathways. Moreover, their expression was liver-specific. 13 hub genes were screened, which were closely related to immune cells in hepatoblastoma tissues. Among them, it was confirmed that AXIN2, LAMB1 and NOTUM were up-regulated and SERPINC1 was down-regulated in hepatoblastoma than normal tissues. NOTUM knockdown distinctly weakened migration and invasion of HuH-6 and HepG2 cells and tumor growth in vivo.Conclusions: This study identified aberrantly methylated and expressed signatures that were in relation to immune microenvironment in hepatoblastoma. Targeting NOTUM hub gene could suppress migration and invasion of hepatoblastoma cells. Thus, these aberrantly methylated and expressed genes might act as therapeutic agents in hepatoblastoma therapy. [ABSTRACT FROM AUTHOR]

Background: Intramuscular fat (IMF) is associated with meat quality and insulin resistance in animals. Research on genetic mechanism of IMF decomposition has positive meaning to pork quality and diseases such as obesity and type 2 diabetes treatment. In this study, an IMF trait segregation population was used to perform RNA sequencing and to analyze the joint or independent effects of genes and long intergenic non-coding RNAs (lincRNAs) on IMF. Results: A total of 26 genes including six lincRNA genes show significantly different expression between high- and low-IMF pigs. Interesting, one lincRNA gene, named IMF related lincRNA (IRLnc) not only has a 292-bp conserved region in 100 vertebrates but also has conserved up and down stream genes (< 10 kb) in pig and humans. Real-time quantitative polymerase chain reaction (RT-qPCR) validation study indicated that nuclear receptor subfamily 4 group A member 3 (NR4A3) which located at the downstream of IRLnc has similar expression pattern with IRLnc. RNAi-mediated loss of function screens identified that IRLnc silencing could inhibit both of the RNA and protein expression of NR4A3. And the in-situ hybridization co-expression experiment indicates that IRLnc may directly binding to NR4A3. As the NR4A3 could regulate the catecholamine catabolism, which could affect insulin sensitivity, we inferred that IRLnc influence IMF decomposition by regulating the expression of NR4A3. Conclusions: In conclusion, a novel functional noncoding variation named IRLnc has been found contribute to IMF by regulating the expression of NR4A3. These findings suggest novel mechanistic approach for treatment of insulin resistance in human beings and meat quality improvement in animal. [ABSTRACT FROM AUTHOR]

Background: In 1997, the Radiation Therapy Oncology Group (RTOG) put forward the recursive partitioning analysis classification for the prognosis of brain metastases (BMs), but this system does not take into account the epidermal growth factor receptor (EGFR) mutations. The aim of the study is to assess the prognosis of patients with EGFR-mutated non-small cell lung cancer (NSCLC) and BMs in the era of tyrosine kinase inhibitor (TKI) availability.Methods: This was a retrospective study of consecutive patients with EGFR-mutated (exon 19 or 21) NSCLC diagnosed between 01/2011 and 12/2014 at the Tianjin Medical University Cancer Institute & Hospital and who were ultimately diagnosed with BMs. The patients were stage I-III at initial presentation and developed BMs as the first progression. Overall survival (OS), OS after BM diagnosis (mOS), intracranial progression-free survival (iPFS), response to treatment, and adverse reactions were analyzed.Results: Median survival was 35 months, and the 1- and 2- year survival rates were 95.6% (108/113) and 74.3% (84/113). The 3-month CR + PR rates of radiotherapy(R), chemotherapy(C), targeted treatment(T), and targeted treatment + radiotherapy(T+R) after BMs were 63.0% (17/27), 26.7% (4/15), 50.0% (7/14), and 89.7% (35/39), respectively. The median survival of the four treatments was 20, 9, 12, and 25 months after BMs, respectively (P = 0.001). Multivariable analysis showed that < 3 BMs (odds ratio (OR) = 3.34, 95% confidence interval (CI): 1.89-5.91, P < 0.001) and treatment after BMs (OR = 0.68, 95%CI: 0.54-0.85, P = 0.001) were independently associated with better prognosis.Conclusions: The prognosis of patients with NSCLC and EGFR mutation in exon 19 or 21 after BM is associated with the number of brain metastasis and the treatment method. Targeted treatment combined with radiotherapy may have some advantages over other treatments, but further study is warranted to validate the results. [ABSTRACT FROM AUTHOR]