This SuperSeries is composed of the SubSeries listed below.
Omics-based Investigation of Diet-induced Obesity Synergized with HBx, Src, and p53 Mutation Accelerating Hepatocarcinogenesis in Zebrafish Model.
Specimen part
View SamplesPrevious studies have identified liver cancer associated to NASH, diabetes, obesity, and some genetic risk factors. We want to investigate the synergism between diet and genetic risk factors in hepatocarcinogenesis using omics data of four background zebrafish in three types of diet. We found the fishes have more genetic risk factors at the same time, and have higher probability to accelerate cancer formation. Overfed and high fat diet will increase the chance. Moreover, the results showed metabolism and genetic information processing, including the pathways of fatty acid metabolism, steroid biosynthesis and ribosome biogenesis are highly affected in hepatocellular carcinoma.
Omics-based Investigation of Diet-induced Obesity Synergized with HBx, Src, and p53 Mutation Accelerating Hepatocarcinogenesis in Zebrafish Model.
Specimen part
View SamplesAnalysis of P4N treated THP-1 cells at gene expression level. The hypothesis in the present study was that low dose P4N influence the activation of monocyte. Results provide important information of the response of monocyte activation, such as cytokine genes and growth factors genes.
In vivo amelioration of endogenous antitumor autoantibodies via low-dose P4N through the LTA4H/activin A/BAFF pathway.
Specimen part, Cell line
View SamplesTo identify genes whose expression was affected by RBP2, we performed gene expression microarray analysis in control and RBP2 depletion human lung cancer cell line. Two individual shRNA (RBP2 KD1 and RBP2 KD2) were used to limit potential off-target effects.
Histone demethylase RBP2 promotes lung tumorigenesis and cancer metastasis.
Cell line
View SamplesCalactin is a small molecule isolated from the Chinese herb Asclepias curassavica. We found that calactin induced DNA damage, G2/M arrest of cell cycle, and apoptosis. The calactin also increased the H2AX and Chk2 phosphorylation, which resulted in the decrease of Cdc25C and cdk1 expressions, indicating that calactin-induced G2/M arrest. Moreover, we observed that calactin-induced DNA fragmentation (DNA ladder), PARP cleavage, increase in Bad and Bax levels, and decrease in Bcl-2 and Bcl-xl expressions, which results in apoptosis. Furthermore, calactin modulates the histone modification enzymes Aurora B, SET8, MSK1, PCAF, and Gcn5, which result in H3K9, H3K18, and H3K23 acetylation, H3S10 and H3S28 phosphorylation, and H4K20 methylation. Docking results showed that calactin has a tendency to bind the active site of TOP1.
No associated publication
Cell line
View SamplesScreening small molecules and drugs for activity to modulate alternative splicing, we found that amiloride, distinct from four other intracellular pH-affecting analogues, could normalize the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts in human hepatocellular carcinoma Huh-7 cells. To elucidate the underlying mechanisms, our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF and also decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, while increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulated kinases and up-regulated phosphatases in the signal pathways known to affect the splicing factor protein phosphorylation. The amiloride effects of splicing factor protein hypo-phosphorylation andnormalizedoncogenic RNA splicing were both abrogated by pre-treatment with a PP1 inhibitor. We then performed global exon array analysis of Huh-7 cells treated with amiloride for 24 hours. Using gene array chips (Affymetrix GeneChip Human Exon 1.0 ST Array of >518000 exons of 42974 genes) for exon array analysis (set parameters of correlation coefficient 0.7, splicing index -1.585 , and log2 ratio -1.585), we found that amiloride influenced the splicing patterns of 551 genes involving at least 584 exons, which included 495 known protein-coding genes involving 526 exons, many of which play key roles in functional networks of ion transport, extracellular matrix, cytoskeletons and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of abnormal RNA splicing for cancer therapeutics.
Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells.
Cell line
View SamplesTime-course analysis of adipocyte gene expression profiles response to high fat diet. The hypothesis tested in the present study was that in diet-induced obesity, early activation of TLR-mediated inflammatory signaling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of a diet-induced obesity.
Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity.
Age, Specimen part, Treatment, Time
View SamplesThe treatment strategy of rectal cancer has substantially changed in recent decades. Historically postoperative chemoradiotherapy (CRT) was considered to be the first-line therapy for stage II and III rectal cancers. However, the preoperative CRT is now considered to be the optimal therapy regimen for locally advanced rectal ancer due to its improved local control, reduced toxicity, and increased rate of sphincter preservation. Our study established a clinically practical multi-class prediction model by adopting a novel strategy that applies two separate prediction models (MI and TO predictor) sequentially to a patient to predict the response. For promising clinical practice, we validated our model in a published dataset, which is completely independent dataset from ours. This study suggests a clinically plausible prediction model that correctly infers the preoperative CRT response of patients with high accuracy based on 163 gene signatures we identified.
No associated publication
Sex, Age
View SamplesDrug-induced alterations in transcriptional regulation play a central role in establishing the persistent neuroplasticities that occur during drug addiction. Additionally, changes in gene expression associated with drug administration provide valuable insight into the molecular basis of drug abuse. The molecular mechanisms that underlie susceptibility to psychostimulant addiction remain unknown. Identifying the common gene transcriptional responses to psychostimulants can provide a mechanistic insight to elucidate the molecular nature of drug dependence.
Neuronal development genes are key elements mediating the reinforcing effects of methamphetamine, amphetamine, and methylphenidate.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy.
Sex, Specimen part
View Samples