Because pancreatic cancer(PC) historically has had poor prognosis and five year survival rates,it has been intensely investigated.Analysis of PC incidence and biology has shown a link between different risk factors su...Because pancreatic cancer(PC) historically has had poor prognosis and five year survival rates,it has been intensely investigated.Analysis of PC incidence and biology has shown a link between different risk factors such as smoking,alcoholism,and obesity and disease progression.Important factors affecting PC include the epigenomic changes driven by DNA methylation and histone acetylation,and actions of microRNA inducing oncogenic or tumor suppressor effects.Studies have identified markers whose dysregulation seem to play important roles in PC progression.PC markers involve classical histone deacetylases(HDAC),PC stem cell(PCSC),and leptin.In this review,we discuss the role of several PC biomarkers,and the potential crosstalk between HDAC,microRNA,and leptin in PC progression.Dysregulated expression of these molecules can increase proliferation,survival,PCSC,resistance to chemotherapy and tumor angiogenesis.The potential relationships between these molecules are further analyzed using data from The Cancer Genome Atlas and crosstalk pathways generated by the Pathway Studio Platform(Ariadne Genomics,Inc.).Oncogenic miRNA21 and tumor suppressor miRNA200 have been previously linked to leptin signaling.Preliminary analysis of PC biopsies and signaling crosstalk suggests that the main adipokine leptin could affect the expression of microRNA and HDAC in PC.Data analysis suggests that HDAC-microRNA-leptin signaling crosstalk may be a new target for PC therapy.展开更多
基金Supported by NIH/NCI,No.1R41CA183399-01A1Department of Defense(DoD) office of the Congressionally Directed Medical Research Programs(CDMRP),No.DODXWH-13-1-0382+7 种基金the DOD W81XWH-13-1-0382NIH/SBIR1R41CA183399-01A1Pilot Project Award from MSM/Tuskegee University/UAB Cancer Center Partnership grant 5U54CA118638PC SPORE Grant from UAB to RRGPNational Institute on Minority Health and Health Disparities(NIMHD)of NIH under award number 5S21MD00101facilities and support services at MSM(1G12RR026250-03NIH RR 03034 and 1C06 RR18386)The Calvin Johnson Jr.Foundation Pancreatic Cancer Research Scholarship to Cynthia I Tchio Mantho
文摘Because pancreatic cancer(PC) historically has had poor prognosis and five year survival rates,it has been intensely investigated.Analysis of PC incidence and biology has shown a link between different risk factors such as smoking,alcoholism,and obesity and disease progression.Important factors affecting PC include the epigenomic changes driven by DNA methylation and histone acetylation,and actions of microRNA inducing oncogenic or tumor suppressor effects.Studies have identified markers whose dysregulation seem to play important roles in PC progression.PC markers involve classical histone deacetylases(HDAC),PC stem cell(PCSC),and leptin.In this review,we discuss the role of several PC biomarkers,and the potential crosstalk between HDAC,microRNA,and leptin in PC progression.Dysregulated expression of these molecules can increase proliferation,survival,PCSC,resistance to chemotherapy and tumor angiogenesis.The potential relationships between these molecules are further analyzed using data from The Cancer Genome Atlas and crosstalk pathways generated by the Pathway Studio Platform(Ariadne Genomics,Inc.).Oncogenic miRNA21 and tumor suppressor miRNA200 have been previously linked to leptin signaling.Preliminary analysis of PC biopsies and signaling crosstalk suggests that the main adipokine leptin could affect the expression of microRNA and HDAC in PC.Data analysis suggests that HDAC-microRNA-leptin signaling crosstalk may be a new target for PC therapy.
