Project description:Under hypoxic condition, solid tumor cells are known to involve gene expressions for adopting low O2 condition. We examined chronic hypoxia environment of human rhabdomyosarcoma cell (SJRH30), which is important for understanding characteristic of cancer in the body. We used microarrays to detail time development of gene expression by using new gene-set analysis called GSMTA and identified up/down-regulated gene sets during hypoxic stress.
Project description:Under hypoxic condition, solid tumor cells are known to involve gene expressions for adopting low O2 condition. We examined chronic hypoxia environment of human rhabdomyosarcoma cell (SJRH30), which is important for understanding characteristic of cancer in the body. We used microarrays to detail time development of gene expression by using new gene-set analysis called GSMTA and identified up/down-regulated gene sets during hypoxic stress. We measured gene expressions at four time-points during 24 hours (0h, 6h, 12h and 24h) under 1% hypoxic condition by Affymetrix GeneChip. GSMTA identified novel differentially-expressed gene set under hypoxic stress at each time point.
Project description:Pancreatic cancer is an aggressive malignancy, characterized by extensive desmoplasia and a hypoxic tumor microenvironment that contributes to therapy resistance. MYB, a proto-oncogene encoding a transcription factor, plays a crucial role in pancreatic tumor growth, metastasis, and desmoplasia. Recently, we also revealed a role of MYB in hypoxic survival of pancreatic cancer by promoting metabolic reprogramming through interaction with HIF1α, modulating its expression and influencing its binding to glycolytic gene promoters. In this study, we examined the impact of hypoxia on the genome-wide occupancy of MYB by performing chromatin immunoprecipitation sequencing (ChIP-seq) analysis. We also used HIF1A knockout cells to investigate the role of HIF1α in altered genomic occupancy of MYB. In addition, we examined the genomic distribution of HIF1α in presence and absence of MYB and the impact of their crosstalk on transcriptional reprogramming and associated signaling alterations by RNA-seq and pathway analyses. Our findings show that hypoxia induces significant changes in MYB’s genomic distribution, partially dependent on HIF1α, and that MYB facilitates HIF1α binding to specific gene promoters. We also identify a subset of hypoxia-induced genes co-regulated by MYB and HIF1α, involved in oncogenic signaling pathways critical for hypoxic adaptation. These results highlight the reciprocal crosstalk between MYB and HIF1α, providing novel mechanistic insights into pancreatic cancer adaptation under hypoxia and suggesting MYB as a potential therapeutic target.
