Pancreatic cancer is a malignancy arising from the endocrine or exocrine compartment of this organ. Tumors from exocrine origin comprise over 90% of all pancreatic cancers diagnosed. Of these, pancreatic ductal adenocarcinoma (PDAC) is the most common histological subtype. The five-year survival rate for PDAC ranged between 5 and 9% for over four decades, and only recently saw a modest increase to ∼12-13%, making this a severe and lethal disease. Like other cancers, PDAC initiation stems from genetic changes. However, therapeutic targeting of PDAC genetic drivers has remained relatively unsuccessful, thus the focus in recent years has expanded to the non-genetic factors underlying the disease pathogenesis. Specifically, it has been proposed that dynamic changes in the epigenetic landscape promote tumor growth and metastasis. Emphasis has been given to the re-organization of enhancers, essential regulatory elements controlling oncogenic gene expression, commonly marked my histone 3 lysine 4 monomethylation (H3K4me1). H3K4me1 is typically deposited by histone lysine methyltransferases (KMTs). While well characterized as oncogenes in other cancer types, recent work has expanded the role of KMTs as tumor suppressor in pancreatic cancer. Here, we review the role and translational significance for PDAC development and therapeutics of KMTs.

中文翻译：

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深入了解 H3K4 KMT 在胰腺癌中驱动的机制。


胰腺癌是起源于该器官的内分泌或外分泌室的恶性肿瘤。外分泌源性肿瘤占所有已诊断胰腺癌的 90% 以上。其中，胰腺导管腺癌（PDAC）是最常见的组织学亚型。四十多年来，PDAC 的五年生存率在 5% 至 9% 之间，直到最近才略有上升至 12-13%，使其成为一种严重且致命的疾病。与其他癌症一样，PDAC 的发生源于基因变化。然而，针对 PDAC 遗传驱动因素的治疗靶向仍然相对不成功，因此近年来的焦点已扩展到疾病发病机制背后的非遗传因素。具体来说，有人提出表观遗传景观的动态变化促进肿瘤生长和转移。重点是增强子的重组，增强子是控制致癌基因表达的重要调控元件，通常标记为组蛋白 3 赖氨酸 4 单甲基化 (H3K4me1)。 H3K4me1 通常由组蛋白赖氨酸甲基转移酶 (KMT) 沉积。虽然 KMT 在其他癌症类型中被充分表征为癌基因，但最近的工作扩大了 KMT 作为胰腺癌肿瘤抑制因子的作用。在这里，我们回顾了 KMT 在 PDAC 开发和治疗中的作用和转化意义。