The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathway
Abstract Purpose Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-11-01
|
| Series: | Cell Division |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13008-024-00136-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849221066387357696 |
|---|---|
| author | Yawen Liu Juanjuan Zhou Weiqi Liu Yi Le Lingling Zhang Ziyu Zhang Ling Zhou Ling Li |
| author_facet | Yawen Liu Juanjuan Zhou Weiqi Liu Yi Le Lingling Zhang Ziyu Zhang Ling Zhou Ling Li |
| author_sort | Yawen Liu |
| collection | DOAJ |
| description | Abstract Purpose Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting the progression of various cancers. This article aims to elucidate the role of RNF6 in CC and its regulation of the Hippo-YAP1 signaling pathway. Methods The public tumor dataset analyses, immunohistochemistry, and western blotting were used to explore the expression of RNF6 in CC. Gain- and loss-of-function assays were conducted to elucidate the role of RNF6 in the proliferation and invasion of CC cells. Transcriptome sequencing was used to explore RNF6’s role in cervical cancer, with validation of its regulation of the Hippo-YAP1 pathway through western blotting and RT-qPCR. Co-transfection of YAP overexpression plasmids into RNF6-silenced CC cells were preformed to confirm YAP1’s pivotal role in RNF6-mediated CC progression. Animal experiments were preformed to further validate RNF6 interference’s inhibitory effect on CC proliferation in vivo. Results Clinical samples and bioinformatics analysis revealed high expression of RNF6 in CC, and closely associated with advanced FIGO (International Federation of Gynecology and Obstetrics) stage, larger tumor size, and poor prognosis. Cellular functional experiments demonstrate that RNF6 promotes the proliferation, invasion, and migration of CC cells, while knockdown of RNF6 yields the opposite effect. Transcriptome sequencing further reveals that RNF6 may promote CC progression through the Hippo-YAP signaling pathway. Western blotting and RT-qPCR further unveil that RNF6 enhances the upregulation of YAP1 protein levels, thereby activating downstream oncogenes CTGF and CYR61 transcription. Additionally, exogenous overexpression of YAP1 reverses the inhibitory effect of RNF6 silencing on CC proliferation and invasion. Furthermore, RNF6 interference significantly attenuates tumor growth in vivo experiments. Conclusion Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment. |
| format | Article |
| id | doaj-art-4588a9890bb04ddfa39ac1ae8258ca9e |
| institution | Kabale University |
| issn | 1747-1028 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Division |
| spelling | doaj-art-4588a9890bb04ddfa39ac1ae8258ca9e2024-11-24T12:35:34ZengBMCCell Division1747-10282024-11-0119111210.1186/s13008-024-00136-8The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathwayYawen Liu0Juanjuan Zhou1Weiqi Liu2Yi Le3Lingling Zhang4Ziyu Zhang5Ling Zhou6Ling Li7Department of Oncology, Jiangxi Maternal and Child Health HospitalDepartment of Oncology, the First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, the First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, the First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, Jiangxi Maternal and Child Health HospitalDepartment of Oncology, Jiangxi Maternal and Child Health HospitalDepartment of Oncology, the First Affiliated Hospital of Nanchang UniversityDepartment of Oncology, Jiangxi Maternal and Child Health HospitalAbstract Purpose Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting the progression of various cancers. This article aims to elucidate the role of RNF6 in CC and its regulation of the Hippo-YAP1 signaling pathway. Methods The public tumor dataset analyses, immunohistochemistry, and western blotting were used to explore the expression of RNF6 in CC. Gain- and loss-of-function assays were conducted to elucidate the role of RNF6 in the proliferation and invasion of CC cells. Transcriptome sequencing was used to explore RNF6’s role in cervical cancer, with validation of its regulation of the Hippo-YAP1 pathway through western blotting and RT-qPCR. Co-transfection of YAP overexpression plasmids into RNF6-silenced CC cells were preformed to confirm YAP1’s pivotal role in RNF6-mediated CC progression. Animal experiments were preformed to further validate RNF6 interference’s inhibitory effect on CC proliferation in vivo. Results Clinical samples and bioinformatics analysis revealed high expression of RNF6 in CC, and closely associated with advanced FIGO (International Federation of Gynecology and Obstetrics) stage, larger tumor size, and poor prognosis. Cellular functional experiments demonstrate that RNF6 promotes the proliferation, invasion, and migration of CC cells, while knockdown of RNF6 yields the opposite effect. Transcriptome sequencing further reveals that RNF6 may promote CC progression through the Hippo-YAP signaling pathway. Western blotting and RT-qPCR further unveil that RNF6 enhances the upregulation of YAP1 protein levels, thereby activating downstream oncogenes CTGF and CYR61 transcription. Additionally, exogenous overexpression of YAP1 reverses the inhibitory effect of RNF6 silencing on CC proliferation and invasion. Furthermore, RNF6 interference significantly attenuates tumor growth in vivo experiments. Conclusion Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment.https://doi.org/10.1186/s13008-024-00136-8Cervical cancerRNF6YAP1ProliferationInvasion and migration |
| spellingShingle | Yawen Liu Juanjuan Zhou Weiqi Liu Yi Le Lingling Zhang Ziyu Zhang Ling Zhou Ling Li The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathway Cell Division Cervical cancer RNF6 YAP1 Proliferation Invasion and migration |
| title | The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathway |
| title_full | The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathway |
| title_fullStr | The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathway |
| title_full_unstemmed | The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathway |
| title_short | The E3 ubiquitin ligase RNF6 facilitates the progression of cervical cancer by inhibiting the Hippo/Yap pathway |
| title_sort | e3 ubiquitin ligase rnf6 facilitates the progression of cervical cancer by inhibiting the hippo yap pathway |
| topic | Cervical cancer RNF6 YAP1 Proliferation Invasion and migration |
| url | https://doi.org/10.1186/s13008-024-00136-8 |
| work_keys_str_mv | AT yawenliu thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT juanjuanzhou thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT weiqiliu thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT yile thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT linglingzhang thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT ziyuzhang thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT lingzhou thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT lingli thee3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT yawenliu e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT juanjuanzhou e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT weiqiliu e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT yile e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT linglingzhang e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT ziyuzhang e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT lingzhou e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway AT lingli e3ubiquitinligasernf6facilitatestheprogressionofcervicalcancerbyinhibitingthehippoyappathway |