The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway
Abstract Background Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the human body and influence the occurrence and development of various diseases. However, the biological functions of circRNAs in colorectal cancer (CRC) are largely unknown. Methods RT-qPCR was used to detect the ex...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-021-01375-x |
| _version_ | 1819100729321717760 |
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| author | Jiaqi Wang Yi Zhang Hu Song Hang Yin Tao Jiang Yixin Xu Lianyu Liu Hongyu Wang Hong Gao Renhao Wang Jun Song |
| author_facet | Jiaqi Wang Yi Zhang Hu Song Hang Yin Tao Jiang Yixin Xu Lianyu Liu Hongyu Wang Hong Gao Renhao Wang Jun Song |
| author_sort | Jiaqi Wang |
| collection | DOAJ |
| description | Abstract Background Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the human body and influence the occurrence and development of various diseases. However, the biological functions of circRNAs in colorectal cancer (CRC) are largely unknown. Methods RT-qPCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circSPARC. Function-based experiments were performed using circSPARC knockdown and overexpression cell lines in vitro and in vivo, including CCK8, colony formation, transwell and metastasis models. Mechanistically, luciferase reporter assay, western blots, RNA immunoprecipitation (RIP), Chromatin isolation by RNA purification (ChIRP) and immunohistochemical stainings were performed. Results CircSPARC was upregulated in both the tissues and plasma of CRC patients. High expression of circSPARC was associated with advanced TNM stage, lymph node metastases, and poor survival. Silencing circSPARC inhibited CRC cell migration and proliferation in vitro and vivo. Mechanistically, circSPARC sponged miR-485-3p to upregulate JAK2 expression and ultimately contribute to the accumulation of phosphorylated (p)-STAT3. Besides, circSPARC recruited FUS, which facilitated the nuclear translocation of p-STAT3. Conclusions These findings suggest that circSPARC might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for CRC treatment by regulating JAK2/STAT3 pathway. |
| first_indexed | 2024-12-22T01:07:24Z |
| format | Article |
| id | doaj.art-4101756b7fb841c98ee56a12f0849bf1 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-22T01:07:24Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-4101756b7fb841c98ee56a12f0849bf12022-12-21T18:44:03ZengBMCMolecular Cancer1476-45982021-06-0120112010.1186/s12943-021-01375-xThe circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathwayJiaqi Wang0Yi Zhang1Hu Song2Hang Yin3Tao Jiang4Yixin Xu5Lianyu Liu6Hongyu Wang7Hong Gao8Renhao Wang9Jun Song10Department of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityInstitute of Digestive Diseases, Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityInstitute of Digestive Diseases, Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityDepartment of General Surgery, The Affiliated Hospital of Xuzhou Medical UniversityAbstract Background Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the human body and influence the occurrence and development of various diseases. However, the biological functions of circRNAs in colorectal cancer (CRC) are largely unknown. Methods RT-qPCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circSPARC. Function-based experiments were performed using circSPARC knockdown and overexpression cell lines in vitro and in vivo, including CCK8, colony formation, transwell and metastasis models. Mechanistically, luciferase reporter assay, western blots, RNA immunoprecipitation (RIP), Chromatin isolation by RNA purification (ChIRP) and immunohistochemical stainings were performed. Results CircSPARC was upregulated in both the tissues and plasma of CRC patients. High expression of circSPARC was associated with advanced TNM stage, lymph node metastases, and poor survival. Silencing circSPARC inhibited CRC cell migration and proliferation in vitro and vivo. Mechanistically, circSPARC sponged miR-485-3p to upregulate JAK2 expression and ultimately contribute to the accumulation of phosphorylated (p)-STAT3. Besides, circSPARC recruited FUS, which facilitated the nuclear translocation of p-STAT3. Conclusions These findings suggest that circSPARC might serve as a potential diagnostic and prognostic biomarker and a therapeutic target for CRC treatment by regulating JAK2/STAT3 pathway.https://doi.org/10.1186/s12943-021-01375-xColorectal cancercircRNAcircSPARCJAK/STAT signalling pathwayBiomarker |
| spellingShingle | Jiaqi Wang Yi Zhang Hu Song Hang Yin Tao Jiang Yixin Xu Lianyu Liu Hongyu Wang Hong Gao Renhao Wang Jun Song The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway Molecular Cancer Colorectal cancer circRNA circSPARC JAK/STAT signalling pathway Biomarker |
| title | The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway |
| title_full | The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway |
| title_fullStr | The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway |
| title_full_unstemmed | The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway |
| title_short | The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway |
| title_sort | circular rna circsparc enhances the migration and proliferation of colorectal cancer by regulating the jak stat pathway |
| topic | Colorectal cancer circRNA circSPARC JAK/STAT signalling pathway Biomarker |
| url | https://doi.org/10.1186/s12943-021-01375-x |
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