Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21
Radiotherapy with or without concurrent chemotherapy is the standard treatment for nasopharyngeal carcinoma (NPC) patients, whose efficacy is limited partly by intrinsic and acquired radioresistance. DNA methyltransferase 3B (DNMT3B) has been reported to participate in tumorigenesis via DNA methylat...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2020-06-01
|
Series: | Molecular Therapy: Oncolytics |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770520300577 |
id |
doaj-552ec45e528a46449303d1c9f0aff082 |
---|---|
record_format |
Article |
spelling |
doaj-552ec45e528a46449303d1c9f0aff0822020-11-25T03:11:47ZengElsevierMolecular Therapy: Oncolytics2372-77052020-06-0117306319Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21Cheng Wu0Ergang Guo1Jun Ming2Wei Sun3Xin Nie4Lu Sun5Shan Peng6Min Luo7Dongbo Liu8Linli Zhang9Qi Mei10Guoxian Long11Guangyuan Hu12Guoqing Hu13Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, People’s Republic of China; Corresponding author: Guoqing Hu, Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Hubei, Wuhan 430030, China.Radiotherapy with or without concurrent chemotherapy is the standard treatment for nasopharyngeal carcinoma (NPC) patients, whose efficacy is limited partly by intrinsic and acquired radioresistance. DNA methyltransferase 3B (DNMT3B) has been reported to participate in tumorigenesis via DNA methylation, but its role in mediating progression and radioresistance of NPC remains unclear. Therefore, we conducted the following studies to explore the relationship between DNMT3B and NPC. Here, we found that DNMT3B was elevated in NPC tissues and predicted the poor prognosis of NPC patients. We demonstrated for the first time that ionizing radiation could induce DNMT3B, which might be one of the reasons for radioresistance. Silencing of DNMT3B inhibited migration and invasion via suppressing epithelial-mesenchymal transition (EMT) in NPC cells. Furthermore, silencing DNMT3B restored and activated p53 and p21 via DNA demethylation, which led to cell cycle arrest and apoptosis, resulting in increased radiosensitivity of NPC both in vitro and in vivo. DNMT3B functions as a novel oncogene in the radioresistance of NPC through regulating EMT, cell cycle, and apoptosis. Therefore, DNMT3B could be a potential target for NPC treatment.http://www.sciencedirect.com/science/article/pii/S2372770520300577DNMT3Bp53p21DNA methylationnasopharyngeal carcinomaradioresistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cheng Wu Ergang Guo Jun Ming Wei Sun Xin Nie Lu Sun Shan Peng Min Luo Dongbo Liu Linli Zhang Qi Mei Guoxian Long Guangyuan Hu Guoqing Hu |
spellingShingle |
Cheng Wu Ergang Guo Jun Ming Wei Sun Xin Nie Lu Sun Shan Peng Min Luo Dongbo Liu Linli Zhang Qi Mei Guoxian Long Guangyuan Hu Guoqing Hu Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21 Molecular Therapy: Oncolytics DNMT3B p53 p21 DNA methylation nasopharyngeal carcinoma radioresistance |
author_facet |
Cheng Wu Ergang Guo Jun Ming Wei Sun Xin Nie Lu Sun Shan Peng Min Luo Dongbo Liu Linli Zhang Qi Mei Guoxian Long Guangyuan Hu Guoqing Hu |
author_sort |
Cheng Wu |
title |
Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21 |
title_short |
Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21 |
title_full |
Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21 |
title_fullStr |
Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21 |
title_full_unstemmed |
Radiation-Induced DNMT3B Promotes Radioresistance in Nasopharyngeal Carcinoma through Methylation of p53 and p21 |
title_sort |
radiation-induced dnmt3b promotes radioresistance in nasopharyngeal carcinoma through methylation of p53 and p21 |
publisher |
Elsevier |
series |
Molecular Therapy: Oncolytics |
issn |
2372-7705 |
publishDate |
2020-06-01 |
description |
Radiotherapy with or without concurrent chemotherapy is the standard treatment for nasopharyngeal carcinoma (NPC) patients, whose efficacy is limited partly by intrinsic and acquired radioresistance. DNA methyltransferase 3B (DNMT3B) has been reported to participate in tumorigenesis via DNA methylation, but its role in mediating progression and radioresistance of NPC remains unclear. Therefore, we conducted the following studies to explore the relationship between DNMT3B and NPC. Here, we found that DNMT3B was elevated in NPC tissues and predicted the poor prognosis of NPC patients. We demonstrated for the first time that ionizing radiation could induce DNMT3B, which might be one of the reasons for radioresistance. Silencing of DNMT3B inhibited migration and invasion via suppressing epithelial-mesenchymal transition (EMT) in NPC cells. Furthermore, silencing DNMT3B restored and activated p53 and p21 via DNA demethylation, which led to cell cycle arrest and apoptosis, resulting in increased radiosensitivity of NPC both in vitro and in vivo. DNMT3B functions as a novel oncogene in the radioresistance of NPC through regulating EMT, cell cycle, and apoptosis. Therefore, DNMT3B could be a potential target for NPC treatment. |
topic |
DNMT3B p53 p21 DNA methylation nasopharyngeal carcinoma radioresistance |
url |
http://www.sciencedirect.com/science/article/pii/S2372770520300577 |
work_keys_str_mv |
AT chengwu radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT ergangguo radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT junming radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT weisun radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT xinnie radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT lusun radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT shanpeng radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT minluo radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT dongboliu radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT linlizhang radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT qimei radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT guoxianlong radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT guangyuanhu radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 AT guoqinghu radiationinduceddnmt3bpromotesradioresistanceinnasopharyngealcarcinomathroughmethylationofp53andp21 |
_version_ |
1724653097077178368 |