Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage
Abstract Background Cervical cancer (CC) is the third most common gynecological malignancy around the world. Cisplatin is an effective drug, but cisplatin resistance is a vital factor limiting the clinical usage of cisplatin. Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA d...
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doaj-82675ebdc90d4860a8e3f9124a046b952020-11-25T03:34:51ZengBMCHereditas1601-52232020-10-0115711810.1186/s41065-020-00154-wEnhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damageXiaoling Wu0Youwen Zhong1Qing Chen2Xin Zhang3Hua Zhang4Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong UniversitySchool of Economics and Finance, Xi’an Jiaotong UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background Cervical cancer (CC) is the third most common gynecological malignancy around the world. Cisplatin is an effective drug, but cisplatin resistance is a vital factor limiting the clinical usage of cisplatin. Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. This research was to investigate the mechanism of EDC4 on cisplatin resistance in CC. Two human cervical cancer cell lines, HeLa and SiHa, were used to investigate the role of EDC4 on cisplatin resistance in vitro. The knockdown or overexpression of EDC4 or replication protein A (RPA) in HeLa or SiHa cells was performed by transfection. Cell viability was analyzed by MTT assay. The growth of cancer cells was evaluated by colony formation assay. DNA damage was measured by γH2AX (a sensitive DNA damage response marker) immunofluorescent staining. The binding of EDC4 and RPA was analyzed by immunoprecipitation. Results EDC4 knockdown in cervical cancer cells (HeLa and SiHa) enhanced cisplatin sensitivity and cisplatin induced cell growth inhibition and DNA damage. EDC4 overexpression reduced DNA damage caused by cisplatin and enhanced cell growth of cervical cancer cells. EDC4 could interact with RPA and promote RPA phosphorylation. RPA knockdown reversed the inhibitory effect of EDC4 on cisplatin-induced DNA damage. Conclusion The present results indicated that EDC4 is responsible for the cisplatin resistance partly through interacting with RPA in cervical cancer by alleviating DNA damage. This study indicated that EDC4 or RPA may be novel targets to combat chemotherapy resistance in cervical cancer. Graphical abstracthttp://link.springer.com/article/10.1186/s41065-020-00154-wCervical CancerCisplatin resistanceEnhancer of mRNA decapping protein 4 (EDC4)Replication protein a (RPA)DNA damage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoling Wu Youwen Zhong Qing Chen Xin Zhang Hua Zhang |
spellingShingle |
Xiaoling Wu Youwen Zhong Qing Chen Xin Zhang Hua Zhang Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage Hereditas Cervical Cancer Cisplatin resistance Enhancer of mRNA decapping protein 4 (EDC4) Replication protein a (RPA) DNA damage |
author_facet |
Xiaoling Wu Youwen Zhong Qing Chen Xin Zhang Hua Zhang |
author_sort |
Xiaoling Wu |
title |
Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage |
title_short |
Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage |
title_full |
Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage |
title_fullStr |
Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage |
title_full_unstemmed |
Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage |
title_sort |
enhancer of mrna decapping protein 4 (edc4) interacts with replication protein a (rpa) and contributes to cisplatin resistance in cervical cancer by alleviating dna damage |
publisher |
BMC |
series |
Hereditas |
issn |
1601-5223 |
publishDate |
2020-10-01 |
description |
Abstract Background Cervical cancer (CC) is the third most common gynecological malignancy around the world. Cisplatin is an effective drug, but cisplatin resistance is a vital factor limiting the clinical usage of cisplatin. Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. This research was to investigate the mechanism of EDC4 on cisplatin resistance in CC. Two human cervical cancer cell lines, HeLa and SiHa, were used to investigate the role of EDC4 on cisplatin resistance in vitro. The knockdown or overexpression of EDC4 or replication protein A (RPA) in HeLa or SiHa cells was performed by transfection. Cell viability was analyzed by MTT assay. The growth of cancer cells was evaluated by colony formation assay. DNA damage was measured by γH2AX (a sensitive DNA damage response marker) immunofluorescent staining. The binding of EDC4 and RPA was analyzed by immunoprecipitation. Results EDC4 knockdown in cervical cancer cells (HeLa and SiHa) enhanced cisplatin sensitivity and cisplatin induced cell growth inhibition and DNA damage. EDC4 overexpression reduced DNA damage caused by cisplatin and enhanced cell growth of cervical cancer cells. EDC4 could interact with RPA and promote RPA phosphorylation. RPA knockdown reversed the inhibitory effect of EDC4 on cisplatin-induced DNA damage. Conclusion The present results indicated that EDC4 is responsible for the cisplatin resistance partly through interacting with RPA in cervical cancer by alleviating DNA damage. This study indicated that EDC4 or RPA may be novel targets to combat chemotherapy resistance in cervical cancer. Graphical abstract |
topic |
Cervical Cancer Cisplatin resistance Enhancer of mRNA decapping protein 4 (EDC4) Replication protein a (RPA) DNA damage |
url |
http://link.springer.com/article/10.1186/s41065-020-00154-w |
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