Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma
The transcription factor MYBL2 is widely expressed in proliferating cells. Aberrant expression of MYBL2 contributes to tumor malignancy and is associated with poor patient prognosis. However, the downstream transcriptional network that mediates its oncogenic properties remains elusive. In the presen...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.816070/full |
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| author | Feiliang Zhong Feiliang Zhong Jia Liu Jia Liu Chang Gao Tingting Chen Bo Li Bo Li Bo Li |
| author_facet | Feiliang Zhong Feiliang Zhong Jia Liu Jia Liu Chang Gao Tingting Chen Bo Li Bo Li Bo Li |
| author_sort | Feiliang Zhong |
| collection | DOAJ |
| description | The transcription factor MYBL2 is widely expressed in proliferating cells. Aberrant expression of MYBL2 contributes to tumor malignancy and is associated with poor patient prognosis. However, the downstream transcriptional network that mediates its oncogenic properties remains elusive. In the present study, we observed that MYBL2 was overexpressed in malignant and metastatic melanoma patient samples and that the high expression level of MYBL2 was significantly associated with poor prognosis. A loss-of-function study demonstrated that MYBL2 depletion significantly decreased cell proliferation and migration and prevented cell cycle progression. We also determined that MYBL2 promoted the formation of melanoma stem-like cell populations, indicating its potential as a therapeutic target for treating resistant melanoma. Mechanistically, we constructed an MYBL2 regulatory network in melanoma by integrating RNA-seq and ChIP-seq data. EPPK1, PDE3A, and FCGR2A were identified as three core target genes of MYBL2. Importantly, multivariate Cox regression and survival curve analysis revealed that PDE3A and EPPK1 were negatively correlated with melanoma patient survival; however, FCGR2A was positively correlated with patient survival. Overall, our findings elucidate an MYBL2 regulatory network related to cell proliferation and cancer development in melanoma, suggesting that MYBL2 may be potentially targeted for melanoma diagnosis and treatment. |
| first_indexed | 2024-04-12T16:16:58Z |
| format | Article |
| id | doaj.art-074a651799a3444a9d6fbdc4f30f9d92 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T16:16:58Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-074a651799a3444a9d6fbdc4f30f9d922022-12-22T03:25:42ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.816070816070Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in MelanomaFeiliang Zhong0Feiliang Zhong1Jia Liu2Jia Liu3Chang Gao4Tingting Chen5Bo Li6Bo Li7Bo Li8Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, ChinaCollaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, ChinaFrontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, ChinaCollaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, ChinaLife Science Institute, Jinzhou Medical University, Jinzhou, ChinaSchool of Basic Medicine, Guangdong Medical University, Dongguan, ChinaFrontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, ChinaCollaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin, ChinaLife Science Institute, Jinzhou Medical University, Jinzhou, ChinaThe transcription factor MYBL2 is widely expressed in proliferating cells. Aberrant expression of MYBL2 contributes to tumor malignancy and is associated with poor patient prognosis. However, the downstream transcriptional network that mediates its oncogenic properties remains elusive. In the present study, we observed that MYBL2 was overexpressed in malignant and metastatic melanoma patient samples and that the high expression level of MYBL2 was significantly associated with poor prognosis. A loss-of-function study demonstrated that MYBL2 depletion significantly decreased cell proliferation and migration and prevented cell cycle progression. We also determined that MYBL2 promoted the formation of melanoma stem-like cell populations, indicating its potential as a therapeutic target for treating resistant melanoma. Mechanistically, we constructed an MYBL2 regulatory network in melanoma by integrating RNA-seq and ChIP-seq data. EPPK1, PDE3A, and FCGR2A were identified as three core target genes of MYBL2. Importantly, multivariate Cox regression and survival curve analysis revealed that PDE3A and EPPK1 were negatively correlated with melanoma patient survival; however, FCGR2A was positively correlated with patient survival. Overall, our findings elucidate an MYBL2 regulatory network related to cell proliferation and cancer development in melanoma, suggesting that MYBL2 may be potentially targeted for melanoma diagnosis and treatment.https://www.frontiersin.org/articles/10.3389/fonc.2022.816070/fullmelanomaMYBL2ChIP-seqregulatory networkprognosis |
| spellingShingle | Feiliang Zhong Feiliang Zhong Jia Liu Jia Liu Chang Gao Tingting Chen Bo Li Bo Li Bo Li Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma Frontiers in Oncology melanoma MYBL2 ChIP-seq regulatory network prognosis |
| title | Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma |
| title_full | Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma |
| title_fullStr | Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma |
| title_full_unstemmed | Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma |
| title_short | Downstream Regulatory Network of MYBL2 Mediating Its Oncogenic Role in Melanoma |
| title_sort | downstream regulatory network of mybl2 mediating its oncogenic role in melanoma |
| topic | melanoma MYBL2 ChIP-seq regulatory network prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.816070/full |
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