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

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 e...

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Autores principales: Zheng, Chunying, Ren, Zhen, Chen, Hongliang, Yuan, Xiaorui, Suye, Suye, Yin, Huan, Fu, Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539389/
https://www.ncbi.nlm.nih.gov/pubmed/37779877
http://dx.doi.org/10.7150/jca.86348
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author Zheng, Chunying
Ren, Zhen
Chen, Hongliang
Yuan, Xiaorui
Suye, Suye
Yin, Huan
Fu, Chun
author_facet Zheng, Chunying
Ren, Zhen
Chen, Hongliang
Yuan, Xiaorui
Suye, Suye
Yin, Huan
Fu, Chun
author_sort Zheng, Chunying
collection PubMed
description 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.
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spelling pubmed-105393892023-09-30 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 J Cancer Research Paper 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. Ivyspring International Publisher 2023-08-28 /pmc/articles/PMC10539389/ /pubmed/37779877 http://dx.doi.org/10.7150/jca.86348 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zheng, Chunying
Ren, Zhen
Chen, Hongliang
Yuan, Xiaorui
Suye, Suye
Yin, Huan
Fu, Chun
Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer
title Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer
title_full Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer
title_fullStr Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer
title_full_unstemmed Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer
title_short Reduced FANCE Confers Genomic Instability and Malignant Behavior by Regulating Cell Cycle Progression in Endometrial Cancer
title_sort reduced fance confers genomic instability and malignant behavior by regulating cell cycle progression in endometrial cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539389/
https://www.ncbi.nlm.nih.gov/pubmed/37779877
http://dx.doi.org/10.7150/jca.86348
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