Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resi
- PDF / 4,192,573 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 118 Downloads / 175 Views
RESEARCH
Open Access
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 Xiaoling Wu1* , Youwen Zhong2, Qing Chen1, Xin Zhang1 and Hua Zhang1
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. Keywords: Cervical Cancer, Cisplatin resistance, Enhancer of mRNA decapping protein 4 (EDC4), Replication protein a (RPA), DNA damage
Background Cervical cancer (CC) is the third most common gynecological malignancy around the world. About onethird of the new cases are found in China, and showing an increasing incidence rate of young patients and early stages * Correspondence: [email protected] 1 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xincheng District, Xi’an City 710004, Shaanxi Province, China Full list of author information is available at the end of the article
every year [1–3]. Although the prevention and treatment have been improved recently, but the prognosis of advanced cervical cancer is poor and prone to recurrence and metastasis [4, 5]. Cisplatin (Cis-Dichlorodiamineplatinum, CDDP) is a commonly used chemotherapeutic agent in clinic and one of the most effective drugs for treatment of advanced or recurrent CC. At the beginning of CC, patients treated with cisplatin got good effect, but many patient
Data Loading...
