Tchio Mantho Cynthia I, Harbuzariu Adriana, Gonzalez-Perez Ruben R
Cynthia I Tchio Mantho, Adriana Harbuzariu, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
World J Clin Oncol. 2017 Jun 10;8(3):178-189. doi: 10.5306/wjco.v8.i3.178.
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.
由于胰腺癌（PC）历来预后较差且五年生存率低，因此受到了深入研究。对胰腺癌发病率和生物学特性的分析表明，吸烟、酗酒和肥胖等不同风险因素与疾病进展之间存在联系。影响胰腺癌的重要因素包括由DNA甲基化和组蛋白乙酰化驱动的表观基因组变化，以及诱导致癌或肿瘤抑制作用的微小RNA的作用。研究已经确定了一些失调似乎在胰腺癌进展中起重要作用的标志物。胰腺癌标志物涉及经典组蛋白去乙酰化酶（HDAC）、胰腺癌干细胞（PCSC）和瘦素。在本综述中，我们讨论了几种胰腺癌生物标志物的作用，以及HDAC、微小RNA和瘦素在胰腺癌进展中的潜在相互作用。这些分子的失调表达可增加细胞增殖、存活、胰腺癌干细胞数量、对化疗的抗性和肿瘤血管生成。利用来自癌症基因组图谱的数据以及通路工作室平台（Ariadne基因组学公司）生成的相互作用通路，进一步分析了这些分子之间的潜在关系。致癌性微小RNA21和肿瘤抑制性微小RNA200先前已与瘦素信号传导相关联。对胰腺癌活检和信号相互作用的初步分析表明，主要脂肪因子瘦素可能影响胰腺癌中微小RNA和HDAC的表达。数据分析表明，HDAC-微小RNA-瘦素信号相互作用可能是胰腺癌治疗的新靶点。
