PTC Therapeutics, Inc., South Plainfield, New Jersey, New Jersey 07080, USA.
J Cell Biochem. 2011 Oct;112(10):2729-41. doi: 10.1002/jcb.23234.
Growing evidence has demonstrated that clonogenic cancer stem (initiating) cells are responsible for tumor regrowth and disease relapse. Bmi-1 plays a critical role in the self-renewal of adult stem cells. The Bmi-1 protein is elevated in many types of cancers, and experimental reduction of Bmi-1 protein levels by small interfering RNA (siRNA) causes apoptosis and/or senescence in tumor cells in vitro and increases susceptibility to cytotoxic agents. The Bmi-1 protein has no known enzymatic activity, but serves as the key regulatory component of the PRC1 complex (polycomb repressive complex-1). This complex influences chromatin structure and regulates transcriptional activity of a number of important loci including the Ink4a locus which encodes the tumor suppressor proteins p16(Ink4a) and p14(Arf) . In this prospective study, we will discuss the implication of BMI1 in cancers, the biology of BMI1, and the regulatory control of BMI1 expression. The target validation and the future prospects of targeting BMI1 in cancer therapy are also discussed.
越来越多的证据表明，克隆形成的癌症干细胞（起始）细胞是肿瘤复发和疾病复发的原因。Bmi-1 在成体干细胞的自我更新中发挥着关键作用。Bmi-1 蛋白在许多类型的癌症中升高，通过小干扰 RNA（siRNA）实验降低 Bmi-1 蛋白水平会导致肿瘤细胞体外凋亡和/或衰老，并增加对细胞毒性药物的敏感性。Bmi-1 蛋白没有已知的酶活性，但作为 PRC1 复合物（多梳抑制复合物-1）的关键调节成分。该复合物影响染色质结构，并调节包括 Ink4a 基因座在内的许多重要基因座的转录活性，该基因座编码肿瘤抑制蛋白 p16(Ink4a)和 p14(Arf)。在这项前瞻性研究中，我们将讨论 BMI1 在癌症中的意义、BMI1 的生物学特性以及 BMI1 表达的调控。还讨论了针对 BMI1 进行癌症治疗的靶标验证和未来前景。
