Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma
Abstract Background Cyclin B2 (CCNB2), a member of the cyclin family, is an oncogene in multiple cancers, including nasopharyngeal carcinoma (NPC). However, the epigenetics mechanism for CCNB2 overexpression in NPC remains unclear. This study dissects the regulatory role of CCNB2 in NPC and the mole...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11768-4 |
| _version_ | 1797363174343704576 |
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| author | Qinsong Liu Yong Yuan Xiaofen Shang Lu Xin |
| author_facet | Qinsong Liu Yong Yuan Xiaofen Shang Lu Xin |
| author_sort | Qinsong Liu |
| collection | DOAJ |
| description | Abstract Background Cyclin B2 (CCNB2), a member of the cyclin family, is an oncogene in multiple cancers, including nasopharyngeal carcinoma (NPC). However, the epigenetics mechanism for CCNB2 overexpression in NPC remains unclear. This study dissects the regulatory role of CCNB2 in NPC and the molecular mechanism. Methods Differentially methylated genes (DMG) and differentially expressed genes (DEG) were screened out in GSE52068 and GSE13597 databases, respectively, and candidate targets were identified by the Venn diagram. GO annotation and pathway enrichment analyses were performed on selected DMG and DEG, and a PPI network was constructed to pinpoint hub genes. PCR and qMSP were conducted to detect the expression and methylation of CCNB2 in cells. The siRNA targeting CCNB2 was transfected into NPC cells, and the migration, proliferation, cell cycle, epithelial-mesenchymal transition (EMT), tumorigenesis, and metastasis were examined. The upstream factor responsible for CCNB2 overexpression in NPC was explored. The p53 activity in NPC cells was assessed using western blot analysis. Results CCNB2 showed hypomethylation and overexpression in NPC. CCNB2 silencing inhibited cell migration, proliferation, cell cycle entry, and EMT. JMJD6 was overexpressed in NPC and upregulated CCNB2 through demethylation. JMJD6 reversed the effects of CCNB2 downregulation, resulting in elevated cellular activity in vitro and tumorigenic and metastatic activities in vivo. CCNB2 blocked the p53 pathway, while the p53 pathway inhibitor reversed the effect of CCNB2 silencing to increase the activity of NPC cells. Conclusions JMJD6 enhanced CCNB2 transcription by demethylating CCNB2, thereby repressing the p53 pathway and promoting NPC progression. |
| first_indexed | 2024-03-08T16:17:10Z |
| format | Article |
| id | doaj.art-36158c6f41ff401f8b615ea58b83a2e8 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-08T16:17:10Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-36158c6f41ff401f8b615ea58b83a2e82024-01-07T12:30:24ZengBMCBMC Cancer1471-24072024-01-0124111410.1186/s12885-023-11768-4Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinomaQinsong Liu0Yong Yuan1Xiaofen Shang2Lu Xin3Department of Otolaryngology, Qingdao Municipal HospitalDepartment of Otolaryngology, Qingdao Municipal HospitalDepartment of Otolaryngology, Qingdao Municipal HospitalDepartment of Otolaryngology, Qingdao Municipal HospitalAbstract Background Cyclin B2 (CCNB2), a member of the cyclin family, is an oncogene in multiple cancers, including nasopharyngeal carcinoma (NPC). However, the epigenetics mechanism for CCNB2 overexpression in NPC remains unclear. This study dissects the regulatory role of CCNB2 in NPC and the molecular mechanism. Methods Differentially methylated genes (DMG) and differentially expressed genes (DEG) were screened out in GSE52068 and GSE13597 databases, respectively, and candidate targets were identified by the Venn diagram. GO annotation and pathway enrichment analyses were performed on selected DMG and DEG, and a PPI network was constructed to pinpoint hub genes. PCR and qMSP were conducted to detect the expression and methylation of CCNB2 in cells. The siRNA targeting CCNB2 was transfected into NPC cells, and the migration, proliferation, cell cycle, epithelial-mesenchymal transition (EMT), tumorigenesis, and metastasis were examined. The upstream factor responsible for CCNB2 overexpression in NPC was explored. The p53 activity in NPC cells was assessed using western blot analysis. Results CCNB2 showed hypomethylation and overexpression in NPC. CCNB2 silencing inhibited cell migration, proliferation, cell cycle entry, and EMT. JMJD6 was overexpressed in NPC and upregulated CCNB2 through demethylation. JMJD6 reversed the effects of CCNB2 downregulation, resulting in elevated cellular activity in vitro and tumorigenic and metastatic activities in vivo. CCNB2 blocked the p53 pathway, while the p53 pathway inhibitor reversed the effect of CCNB2 silencing to increase the activity of NPC cells. Conclusions JMJD6 enhanced CCNB2 transcription by demethylating CCNB2, thereby repressing the p53 pathway and promoting NPC progression.https://doi.org/10.1186/s12885-023-11768-4JMJD6CCNB2p53 pathwayMethylationNasopharyngeal carcinoma |
| spellingShingle | Qinsong Liu Yong Yuan Xiaofen Shang Lu Xin Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma BMC Cancer JMJD6 CCNB2 p53 pathway Methylation Nasopharyngeal carcinoma |
| title | Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma |
| title_full | Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma |
| title_fullStr | Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma |
| title_full_unstemmed | Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma |
| title_short | Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma |
| title_sort | cyclin b2 impairs the p53 signaling in nasopharyngeal carcinoma |
| topic | JMJD6 CCNB2 p53 pathway Methylation Nasopharyngeal carcinoma |
| url | https://doi.org/10.1186/s12885-023-11768-4 |
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