2. Academic Validation
  3. FANCD2 promotes the malignant behavior of endometrial cancer cells and its prognostic value

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

  • Exp Cell Res. 2022 Dec 15;421(2):113388. doi: 10.1016/j.yexcr.2022.113388.
Chunying Zheng 1,  Zhen Ren 1,  Hongliang Chen 1,  Xiaorui Yuan 1,  Suye Suye 1,  Huan Yin 1,  Zhixian Zhou 1,  Chun Fu 2
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
  • 2 Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China. Electronic address: [email protected].
PMID: 36257352 DOI: 10.1016/j.yexcr.2022.113388
Abstract

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.

Keywords

Cell cycle; Chemotherapy sensitivity; DNA damage repair; Endometrial cancer; FANCD2; Proliferation.

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