FANCD2 promotes the malignant behavior of endometrial cancer cells and its prognostic value

被引：14

作者：

Zheng, Chunying ^{[1
]}

Ren, Zhen ^{[1
]}

Chen, Hongliang ^{[1
]}

Yuan, Xiaorui ^{[1
]}

Suye, Suye ^{[1
]}

Yin, Huan ^{[1
]}

Zhou, Zhixian ^{[1
]}

Fu, Chun ^{[1
,2
]}

机构：

[1] Cent South Univ, Xiangya Hosp 2, Dept Obstet & Gynecol, Changsha 410011, Hunan, Peoples R China

[2] 139 Ren Min Rd, Changsha 410011, Hunan, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2022年 / 421卷 / 02期

关键词：

Endometrial cancer; DNA damage repair; FANCD2; Proliferation; Cell cycle; Chemotherapy sensitivity; FANCONI-ANEMIA; PROTEIN; EXPRESSION; CARCINOMA; PATHWAY; SCREEN;

D O I：

10.1016/j.yexcr.2022.113388

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Defective DNA damage repair is a key mechanism affecting tumor susceptibility, treatment response, and sur-vival 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 carcino-genesis 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.

引用

页数：12

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