Project description:Understanding molecular mechanism associated with high altitude exposure during acclimatization/adaptation/maladaptation. Data reveals specific components of the complex molecular circuitry underlying high altitude pulmonary edema. Individualized outcome prediction were constructed through expression profiling of 39400 genes in sea level sojourners who were acclimatized to high altitude and grouped as controls (n=14), high altitude natives (n=14) and individuals who developed high altitude pulmonary edema within 48-72 hours after air induction to high altitude (n=17).
Project description:Understanding molecular mechanism associated with high altitude exposure during acclimatization/adaptation/maladaptation. Data reveals specific components of the complex molecular circuitry underlying high altitude pulmonary edema.
2013-12-18 | GSE52209 | GEO
Project description:Gut microbiota influence high altitude pulmonary edema
Project description:High Altitude Pulmonary Edema (HAPE) is a type of idiopathic non-cardiogenic pulmonary oedema at high altitude with a severe clinical course and high mortality rate. Therefore, this study aims to investigate transcriptomic signatures in HAPE based on whole-transcriptome sequencing. We identified the differential expression of mRNAs, miRNAs, circRNAs, lncRNAs, alternative splicing (AS) events, gene fusions and novel transcripts, constructed ceRNA networks and immune cell infiltration landscapes, and annotated the biological functions of target genes based on bioinformatics analysis. This study will clarify the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identify novel transcripts and genes, increase our understanding of the transcriptional characteristics of HAPE, elucidate disease-associated pathways and biological processes, and provide underlying mechanisms for HAPE diagnosis and treatment.
Project description:In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various stages of the disease. However, therapy resistance inevitably occurs and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multi-omics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from high-risk prostate cancer patients enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors towards a neuroendocrine-like disease state. In addition, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 – from inactive chromatin binding sites towards active cis-regulatory elements that dictate pro-survival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian rhythm core component ARNTL. Post-treatment ARNTL levels associated with poor outcome, and ARNTL suppression decreased cell growth in vitro. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy, and revealed an acquired dependency on circadian regulator ARNTL, a novel candidate therapeutic target.
Project description:We performed ChIP-seq of two core circadian TFs which were found to be important in leukemia proliferation, in order to identify potential target genes regulated by the circadian rhythm. Here, we performed ChIP-seq for the core circadian transcription factors CLOCK and ARNTL (BMAL1) in NOMO-1 and THP-1 cells.
Project description:The circadian clock regulates metabolism and other critical cellular functions. We used CRISPR-Cas9 to knockout the core clock gene Arntl in KPC cells
Project description:In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various stages of the disease. However, therapy resistance inevitably occurs and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multi-omics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from high-risk prostate cancer patients enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors towards a neuroendocrine-like disease state. In addition, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 – from inactive chromatin binding sites towards active cis-regulatory elements that dictate pro-survival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian rhythm core component ARNTL. Post-treatment ARNTL levels associated with poor outcome, and ARNTL suppression decreased cell growth in vitro. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy, and revealed an acquired dependency on circadian regulator ARNTL, a novel candidate therapeutic target.
