Sun Yaoqi, Cheng Zhongping, Liu Shupeng
Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Department of Obstetrics and Gynecology, Putuo District People's Hospital of Shanghai City, Shanghai, 200060, China.
Mol Med. 2022 Oct 27;28(1):128. doi: 10.1186/s10020-022-00555-9.
Aberrant DNA replication is the main source of genomic instability that leads to tumorigenesis and progression. MCM2, a core subunit of eukaryotic helicase, plays a vital role in DNA replication. The dysfunction of MCM2 results in the occurrence and progression of multiple cancers through impairing DNA replication and cell proliferation.
MCM2 is a vital regulator in DNA replication. The overexpression of MCM2 was detected in multiple types of cancers, and the dysfunction of MCM2 was correlated with the progression and poor prognoses of malignant tumors. According to the altered expression of MCM2 and its correlation with clinicopathological features of cancer patients, MCM2 was thought to be a sensitive biomarker for cancer diagnosis, prognosis, and chemotherapy response. The anti-tumor effect induced by MCM2 inhibition implies the potential of MCM2 to be a novel therapeutic target for cancer treatment. Since DNA replication stress, which may stimulate anti-tumor immunity, frequently occurs in MCM2 deficient cells, it also proposes the possibility that MCM2 targeting improves the effect of tumor immunotherapy.
异常的DNA复制是导致肿瘤发生和进展的基因组不稳定的主要来源。MCM2是真核解旋酶的核心亚基,在DNA复制中起关键作用。MCM2功能障碍通过损害DNA复制和细胞增殖导致多种癌症的发生和进展。
MCM2是DNA复制中的关键调节因子。在多种类型的癌症中检测到MCM2过表达,且MCM2功能障碍与恶性肿瘤的进展和不良预后相关。根据MCM2表达的改变及其与癌症患者临床病理特征的相关性,MCM2被认为是癌症诊断、预后和化疗反应的敏感生物标志物。MCM2抑制诱导的抗肿瘤作用暗示了MCM2作为癌症治疗新靶点的潜力。由于DNA复制应激(可能刺激抗肿瘤免疫)在MCM2缺陷细胞中频繁发生,这也提出了靶向MCM2可提高肿瘤免疫治疗效果的可能性。