Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
Exp Cell Res. 2022 Dec 15;421(2):113388. doi: 10.1016/j.yexcr.2022.113388. Epub 2022 Oct 15.
Defective DNA damage repair is a key mechanism affecting tumor susceptibility, treatment response, and survival outcome of endometrial cancer (EC). Fanconi anemia complementation group D2 (FANCD2) is the core component of the Fanconi anemia repair pathway. To explore the function of FANCD2 in EC, we examined the expression of FANCD2 in human specimens and databases, and discussed the possible mechanism of carcinogenesis by in vitro assays. Immunohistochemistry results showed overexpression of FANCD2 was detected in EC tissues compared to normal and atypical hyperplasia endometrium. Higher FANCD2 expression was correlated with deeper myometrial invasion (MI) and proficient mismatch repair status. The Cancer Genome Atlas (TCGA) database analysis showed FANCD2 was upregulated in EC compared with normal tissue. The high expression of FANCD2 was associated with poor overall survival in EC. Knockdown of FANCD2 expression in EC cell lines inhibited malignant proliferation and migration ability. We demonstrated that decreased FANCD2 expression results in increased DNA damage and decreased S-phase cells, leading to a decrease in proliferative capacity in EC cells. Down-regulated FANCD2 confers sensitivity of EC cells to interstrand crosslinking agents. This study provides evidence for the malignant progression and prognostic value of FANCD2 in EC.
DNA 损伤修复缺陷是影响子宫内膜癌（EC）易感性、治疗反应和生存结局的关键机制。范可尼贫血互补组 D2（FANCD2）是范可尼贫血修复途径的核心组成部分。为了探讨 FANCD2 在 EC 中的功能，我们检测了人类标本和数据库中 FANCD2 的表达，并通过体外实验探讨了其致癌的可能机制。免疫组化结果显示，与正常和非典型增生子宫内膜相比，EC 组织中 FANCD2 表达上调。较高的 FANCD2 表达与更深的肌层浸润（MI）和错配修复功能完整相关。癌症基因组图谱（TCGA）数据库分析显示，与正常组织相比，EC 中 FANCD2 表达上调。FANCD2 的高表达与 EC 患者的总生存率降低相关。在 EC 细胞系中敲低 FANCD2 的表达抑制了恶性增殖和迁移能力。我们证明，FANCD2 表达下调导致 DNA 损伤增加和 S 期细胞减少，从而降低 EC 细胞的增殖能力。下调 FANCD2 可使 EC 细胞对链间交联剂敏感。本研究为 FANCD2 在 EC 中的恶性进展和预后价值提供了证据。
