Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer

Zheng, Chunying; Ren, Zhen; Chen, Hongliang; Yuan, Xiaorui; Suye, Suye; Yin, Huan; Fu, Chun

doi:10.7150/jca.86348

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International Journal of Medical Sciences

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Journal of Genomics

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J Cancer 2023; 14(14):2670-2685. doi:10.7150/jca.86348 This issue Cite

Research Paper

Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer

Chunying Zheng, Zhen Ren, Hongliang Chen, Xiaorui Yuan, Suye Suye, Huan Yin, Chun Fu^✉

Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.

Citation:

Zheng C, Ren Z, Chen H, Yuan X, Suye S, Yin H, Fu C. Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer. J Cancer 2023; 14(14):2670-2685. doi:10.7150/jca.86348. https://www.jcancer.org/v14p2670.htm

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Abstract

Introduction: Fanconi anemia complementation group E (FANCE) is a subunit of fanconi anemia (FA) pathway and plays a key role in repairing DNA interstrand cross-links (ICLs) damage. We investigate detailed functions and mechanisms of FANCE in endometrial cancer (EC).

Methods: FANCE protein and RNA expression in EC and non-cancerous tissues were detected by Western blotting (WB), immunohistochemistry (IHC), and real-time polymerase chain reaction (RT-PCR) assays. Using lentiviral transfection and siRNA interference techniques, we constructed overexpressing FANCE (OE-FANCE) and FANCE-knockdown (FANCE-KD) EC cells. We then investigated DNA damage repair capacity of FANCE in EC cells including comet assay and γH2AX immunofluorescence assay. In vitro assays including CCK8, EDU and colony formation for chemoresistance and proliferation, transwell assay for metastasis were performed. Flow cytometer assay, cell cycle synchronization for cell cycle progression and EC cells RNA sequencing were determined. Finally, in vivo mouse models were used to detect tumor growth.

Results: We found FANCE RNA and protein expression was significantly decreased in endometrioid adenocarcinoma (EAC) compared with normal and atypical hyperplasia endometrium. FANCE promoted the repair of ICL damage and double-strand break (DSB) in OE-FANCE EC cells. Furthermore, FANCE increased drug resistance in OE-FANCE EC cells by upregulating FA pathway and homologous recombination (HR) associated proteins. FANCE inhibited cell proliferation and metastasis through G2/M cell cycle arrest in vitro and vivo. FANCE participated in regulating several pathways.

Conclusion: The study demonstrates the reduction of FANCE expression leads to genomic instability, thereby promoting the development of EC by regulating cell cycle.

Keywords: endometrial cancer, FANCE, genomic instability, cell cycle, proliferation, chemoresistance

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APA

Zheng, C., Ren, Z., Chen, H., Yuan, X., Suye, S., Yin, H., Fu, C. (2023). Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer. Journal of Cancer, 14(14), 2670-2685. https://doi.org/10.7150/jca.86348.

ACS

Zheng, C.; Ren, Z.; Chen, H.; Yuan, X.; Suye, S.; Yin, H.; Fu, C. Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer. J. Cancer 2023, 14 (14), 2670-2685. DOI: 10.7150/jca.86348.

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CSE

Zheng C, Ren Z, Chen H, Yuan X, Suye S, Yin H, Fu C. 2023. Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer. J Cancer. 14(14):2670-2685.

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