CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A
Abstract Background Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-03-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-020-06762-z |
| _version_ | 1811214679253450752 |
|---|---|
| author | Nuo Xu Fanglei Liu Shengdi Wu Maosong Ye Haiyan Ge Meiling Zhang Yuanlin Song Lin Tong Jian Zhou Chunxue Bai |
| author_facet | Nuo Xu Fanglei Liu Shengdi Wu Maosong Ye Haiyan Ge Meiling Zhang Yuanlin Song Lin Tong Jian Zhou Chunxue Bai |
| author_sort | Nuo Xu |
| collection | DOAJ |
| description | Abstract Background Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. Methods By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Results Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. Conclusions CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A. |
| first_indexed | 2024-04-12T06:07:56Z |
| format | Article |
| id | doaj.art-08a8d96a20e149e39b0f82fba2ff4519 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T06:07:56Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-08a8d96a20e149e39b0f82fba2ff45192022-12-22T03:44:47ZengBMCBMC Cancer1471-24072020-03-0120111110.1186/s12885-020-06762-zCHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5ANuo Xu0Fanglei Liu1Shengdi Wu2Maosong Ye3Haiyan Ge4Meiling Zhang5Yuanlin Song6Lin Tong7Jian Zhou8Chunxue Bai9Department of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Pulmonary Medicine, Shanghai East Hospital, Tongji UniversityDepartment of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan UniversityDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Pulmonary Medicine, Huadong HospitalDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityDepartment of Pulmonary Medicine, Zhongshan Hospital, Fudan UniversityAbstract Background Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. Methods By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Results Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. Conclusions CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.http://link.springer.com/article/10.1186/s12885-020-06762-zCHD4metastasisnon-small cell lung cancerPHF5Aproliferation |
| spellingShingle | Nuo Xu Fanglei Liu Shengdi Wu Maosong Ye Haiyan Ge Meiling Zhang Yuanlin Song Lin Tong Jian Zhou Chunxue Bai CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A BMC Cancer CHD4 metastasis non-small cell lung cancer PHF5A proliferation |
| title | CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A |
| title_full | CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A |
| title_fullStr | CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A |
| title_full_unstemmed | CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A |
| title_short | CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A |
| title_sort | chd4 mediates proliferation and migration of non small cell lung cancer via the rhoa rock pathway by regulating phf5a |
| topic | CHD4 metastasis non-small cell lung cancer PHF5A proliferation |
| url | http://link.springer.com/article/10.1186/s12885-020-06762-z |
| work_keys_str_mv | AT nuoxu chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT fangleiliu chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT shengdiwu chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT maosongye chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT haiyange chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT meilingzhang chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT yuanlinsong chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT lintong chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT jianzhou chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a AT chunxuebai chd4mediatesproliferationandmigrationofnonsmallcelllungcancerviatherhoarockpathwaybyregulatingphf5a |