The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway
Abstract Background Glioma is the most common and malignant tumor of central nervous system. The tumor initiation, self-renewal, and multi-lineage differentiation abilities of glioma stem cells (GSCs) are responsible for glioma proliferation and recurrence. Although circular RNAs (circRNAs) play vit...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-04-01
|
| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-021-01931-9 |
| _version_ | 1819085032839446528 |
|---|---|
| author | Junshuang Zhao Yang Jiang Haiying Zhang Jinpeng Zhou Lian Chen Hao Li Jinkun Xu Guoqing Zhang Zhitao Jing |
| author_facet | Junshuang Zhao Yang Jiang Haiying Zhang Jinpeng Zhou Lian Chen Hao Li Jinkun Xu Guoqing Zhang Zhitao Jing |
| author_sort | Junshuang Zhao |
| collection | DOAJ |
| description | Abstract Background Glioma is the most common and malignant tumor of central nervous system. The tumor initiation, self-renewal, and multi-lineage differentiation abilities of glioma stem cells (GSCs) are responsible for glioma proliferation and recurrence. Although circular RNAs (circRNAs) play vital roles in the progression of glioma, the detailed mechanisms remain unknown. Methods qRT-PCR, western blotting, immunohistochemistry, and bioinformatic analysis were performed to detect the expression of circATP5B, miR-185-5p, HOXB5, and SRSF1. Patient-derived GSCs were established, and MTS, EDU, neurosphere formation, and limiting dilution assays were used to detect the proliferation of GSCs. RNA-binding protein immunoprecipitation, RNA pull-down, luciferase reporter assays, and chromatin immunoprecipitation assays were used to detect these molecules’ regulation mechanisms. Results We found circATP5B expression was significantly upregulated in GSCs and promoted the proliferation of GSCs. Mechanistically, circATP5B acted as miR-185-5p sponge to upregulate HOXB5 expression. HOXB5 was overexpressed in glioma and transcriptionally regulated IL6 expression and promoted the proliferation of GSCs via JAK2/STAT3 signaling. Moreover, RNA binding protein SRSF1 could bind to and promote circATP5B expression and regulate the proliferation of GSCs, while HOXB5 also transcriptionally regulated SRSF1 expression. Conclusions Our study identified the SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop in GSCs. This provides an effective biomarker for glioma diagnosis and prognostic evaluation. |
| first_indexed | 2024-12-21T20:57:55Z |
| format | Article |
| id | doaj.art-42ac07a5ce1b452ea24bf8120b5b1995 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-21T20:57:55Z |
| publishDate | 2021-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-42ac07a5ce1b452ea24bf8120b5b19952022-12-21T18:50:31ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-04-0140112310.1186/s13046-021-01931-9The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathwayJunshuang Zhao0Yang Jiang1Haiying Zhang2Jinpeng Zhou3Lian Chen4Hao Li5Jinkun Xu6Guoqing Zhang7Zhitao Jing8Department of Neurosurgery, the First Hospital of China Medical UniversityDepartment of Neurosurgery, the First Hospital of China Medical UniversityInternational Education College, Liaoning University of Traditional Chinese MedicineDepartment of Neurosurgery, the First Hospital of China Medical UniversityDepartment of Neurosurgery, the First Hospital of China Medical UniversityDepartment of Neurosurgery, the First Hospital of China Medical UniversityDepartment of Neurosurgery, the First Hospital of China Medical UniversityDepartment of Neurosurgery, the First Hospital of China Medical UniversityDepartment of Neurosurgery, the First Hospital of China Medical UniversityAbstract Background Glioma is the most common and malignant tumor of central nervous system. The tumor initiation, self-renewal, and multi-lineage differentiation abilities of glioma stem cells (GSCs) are responsible for glioma proliferation and recurrence. Although circular RNAs (circRNAs) play vital roles in the progression of glioma, the detailed mechanisms remain unknown. Methods qRT-PCR, western blotting, immunohistochemistry, and bioinformatic analysis were performed to detect the expression of circATP5B, miR-185-5p, HOXB5, and SRSF1. Patient-derived GSCs were established, and MTS, EDU, neurosphere formation, and limiting dilution assays were used to detect the proliferation of GSCs. RNA-binding protein immunoprecipitation, RNA pull-down, luciferase reporter assays, and chromatin immunoprecipitation assays were used to detect these molecules’ regulation mechanisms. Results We found circATP5B expression was significantly upregulated in GSCs and promoted the proliferation of GSCs. Mechanistically, circATP5B acted as miR-185-5p sponge to upregulate HOXB5 expression. HOXB5 was overexpressed in glioma and transcriptionally regulated IL6 expression and promoted the proliferation of GSCs via JAK2/STAT3 signaling. Moreover, RNA binding protein SRSF1 could bind to and promote circATP5B expression and regulate the proliferation of GSCs, while HOXB5 also transcriptionally regulated SRSF1 expression. Conclusions Our study identified the SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop in GSCs. This provides an effective biomarker for glioma diagnosis and prognostic evaluation.https://doi.org/10.1186/s13046-021-01931-9Glioma stem cellsCircATP5BMiR-185-5PHOXB5SRSF1IL6 |
| spellingShingle | Junshuang Zhao Yang Jiang Haiying Zhang Jinpeng Zhou Lian Chen Hao Li Jinkun Xu Guoqing Zhang Zhitao Jing The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway Journal of Experimental & Clinical Cancer Research Glioma stem cells CircATP5B MiR-185-5P HOXB5 SRSF1 IL6 |
| title | The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway |
| title_full | The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway |
| title_fullStr | The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway |
| title_full_unstemmed | The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway |
| title_short | The SRSF1/circATP5B/miR-185-5p/HOXB5 feedback loop regulates the proliferation of glioma stem cells via the IL6-mediated JAK2/STAT3 signaling pathway |
| title_sort | srsf1 circatp5b mir 185 5p hoxb5 feedback loop regulates the proliferation of glioma stem cells via the il6 mediated jak2 stat3 signaling pathway |
| topic | Glioma stem cells CircATP5B MiR-185-5P HOXB5 SRSF1 IL6 |
| url | https://doi.org/10.1186/s13046-021-01931-9 |
| work_keys_str_mv | AT junshuangzhao thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT yangjiang thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT haiyingzhang thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT jinpengzhou thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT lianchen thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT haoli thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT jinkunxu thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT guoqingzhang thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT zhitaojing thesrsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT junshuangzhao srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT yangjiang srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT haiyingzhang srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT jinpengzhou srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT lianchen srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT haoli srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT jinkunxu srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT guoqingzhang srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway AT zhitaojing srsf1circatp5bmir1855phoxb5feedbackloopregulatestheproliferationofgliomastemcellsviatheil6mediatedjak2stat3signalingpathway |