癌症是全球主要死亡原因之一，其发病率和死亡率每年都在上升。对抗癌症的治疗策略有所进展，但仍不足以扭转这一趋势。除了其他几种风险因素外，异常的遗传和表观遗传调控在细胞转化和肿瘤发生中起着关键作用。表观遗传调控因子UHRF1（含PHD和RING指结构域的泛素样蛋白1）是一种多结构域蛋白，在大多数癌症中过度表达并具有致癌能力。通过其多个结构域和其他表观遗传关键参与因子的协同作用，UHRF1调控DNA甲基化和组蛋白修饰。这种良好协调的对话导致肿瘤抑制基因（TSGs）的沉默，并促进肿瘤细胞对抗癌药物的抗性，最终促进凋亡逃逸和无控制增殖。多项研究表明，使用天然化合物下调肿瘤细胞中的UHRF1可导致多个TSGs的重新活化，抑制细胞生长，并促进凋亡。本综述探讨了各种天然和合成化合物的潜力及其机制，这些化合物可以抑制/最小化UHRF1的致癌活性和/或其表达。

Cancer is one of the leading causes of death worldwide, and its incidence and mortality are increasing each year. Improved therapeutic strategies against cancer have progressed, but remain insufficient to invert this trend. Along with several other risk factors, abnormal genetic and epigenetic regulations play a critical role in the initiation of cellular transformation, as well as tumorigenesis. The epigenetic regulator UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is a multidomain protein with oncogenic abilities overexpressed in most cancers. Through the coordination of its multiple domains and other epigenetic key players, UHRF1 regulates DNA methylation and histone modifications. This well-coordinated dialogue leads to the silencing of tumor-suppressor genes (TSGs) and facilitates tumor cells' resistance toward anticancer drugs, ultimately promoting apoptosis escape and uncontrolled proliferation. Several studies have shown that the downregulation of UHRF1 with natural compounds in tumor cells induces the reactivation of various TSGs, inhibits cell growth, and promotes apoptosis. In this review, we discuss the underlying mechanisms and the potential of various natural and synthetic compounds that can inhibit/minimize UHRF1's oncogenic activities and/or its expression.