The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer
Abstract Background Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Efficacy of the bromodomain 4 (BRD4) inhibitor JQ1 has been reported for the treatment of various human cancers, but its potential impact on EC remains unclear. We therefore aimed to eluci...
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03545-x |
| _version_ | 1811222452970192896 |
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| author | Yingxin Pang Gaigai Bai Jing Zhao Xuan Wei Rui Li Jie Li Shunxue Hu Lu Peng Peishu Liu Hongluan Mao |
| author_facet | Yingxin Pang Gaigai Bai Jing Zhao Xuan Wei Rui Li Jie Li Shunxue Hu Lu Peng Peishu Liu Hongluan Mao |
| author_sort | Yingxin Pang |
| collection | DOAJ |
| description | Abstract Background Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Efficacy of the bromodomain 4 (BRD4) inhibitor JQ1 has been reported for the treatment of various human cancers, but its potential impact on EC remains unclear. We therefore aimed to elucidate the function of BRD4 and the effects of JQ1 in EC in vivo and in vitro. Methods The mRNA expression of BRD4 was evaluated using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). BRD4 protein expression in EC tissues was measured using immunohistochemistry (IHC) assays. The effects of JQ1 on EC were determined by using MTT and colony formation assays, flow cytometry and xenograft mouse models. The underlying mechanism was also examined by western blot and small interfering RNA (siRNA) transfection. Results BRD4 was overexpressed in EC tissues, and the level of BRD4 expression was strongly related to poor prognosis. The BRD4-specific inhibitor JQ1 suppressed cell proliferation and colony formation and triggered cell apoptosis, cell cycle arrest, and changes in the expression of proteins in related signaling pathways. Moreover, JQ1 decreased the protein expression of BRD4 and c-Myc, and knockdown of BRD4 or c-Myc reduced the viability of EC cells. Intraperitoneal administration of JQ1 (50 mg/kg) significantly suppressed the tumorigenicity of EC cells in a xenograft mouse model. Conclusion Our results demonstrate that BRD4 is a potential marker of EC and that the BRD4 inhibitor JQ1 is a promising chemotherapeutic agent for the treatment of EC. |
| first_indexed | 2024-04-12T08:16:06Z |
| format | Article |
| id | doaj.art-e803068f9bd24a41a772997e0b471b83 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-12T08:16:06Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-e803068f9bd24a41a772997e0b471b832022-12-22T03:40:48ZengBMCJournal of Translational Medicine1479-58762022-07-0120111710.1186/s12967-022-03545-xThe BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancerYingxin Pang0Gaigai Bai1Jing Zhao2Xuan Wei3Rui Li4Jie Li5Shunxue Hu6Lu Peng7Peishu Liu8Hongluan Mao9Department of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Clinical Laboratory, Qilu Hospital of Shandong UniversityDepartment of Pathology, Qilu Hospital of Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong UniversityAbstract Background Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Efficacy of the bromodomain 4 (BRD4) inhibitor JQ1 has been reported for the treatment of various human cancers, but its potential impact on EC remains unclear. We therefore aimed to elucidate the function of BRD4 and the effects of JQ1 in EC in vivo and in vitro. Methods The mRNA expression of BRD4 was evaluated using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). BRD4 protein expression in EC tissues was measured using immunohistochemistry (IHC) assays. The effects of JQ1 on EC were determined by using MTT and colony formation assays, flow cytometry and xenograft mouse models. The underlying mechanism was also examined by western blot and small interfering RNA (siRNA) transfection. Results BRD4 was overexpressed in EC tissues, and the level of BRD4 expression was strongly related to poor prognosis. The BRD4-specific inhibitor JQ1 suppressed cell proliferation and colony formation and triggered cell apoptosis, cell cycle arrest, and changes in the expression of proteins in related signaling pathways. Moreover, JQ1 decreased the protein expression of BRD4 and c-Myc, and knockdown of BRD4 or c-Myc reduced the viability of EC cells. Intraperitoneal administration of JQ1 (50 mg/kg) significantly suppressed the tumorigenicity of EC cells in a xenograft mouse model. Conclusion Our results demonstrate that BRD4 is a potential marker of EC and that the BRD4 inhibitor JQ1 is a promising chemotherapeutic agent for the treatment of EC.https://doi.org/10.1186/s12967-022-03545-xEndometrial cancerBRD4JQ1Cell apoptosisCell cycle arrestc-Myc |
| spellingShingle | Yingxin Pang Gaigai Bai Jing Zhao Xuan Wei Rui Li Jie Li Shunxue Hu Lu Peng Peishu Liu Hongluan Mao The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer Journal of Translational Medicine Endometrial cancer BRD4 JQ1 Cell apoptosis Cell cycle arrest c-Myc |
| title | The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer |
| title_full | The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer |
| title_fullStr | The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer |
| title_full_unstemmed | The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer |
| title_short | The BRD4 inhibitor JQ1 suppresses tumor growth by reducing c-Myc expression in endometrial cancer |
| title_sort | brd4 inhibitor jq1 suppresses tumor growth by reducing c myc expression in endometrial cancer |
| topic | Endometrial cancer BRD4 JQ1 Cell apoptosis Cell cycle arrest c-Myc |
| url | https://doi.org/10.1186/s12967-022-03545-x |
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