IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis
Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02550-8 |
| _version_ | 1811196652444188672 |
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| author | Chang Wang Mingxia Zhou Peiyu Zhu Chenxi Ju Jinxiu Sheng Dan Du Junhu Wan Huiqing Yin Yurong Xing Hongle Li Jing He Fucheng He |
| author_facet | Chang Wang Mingxia Zhou Peiyu Zhu Chenxi Ju Jinxiu Sheng Dan Du Junhu Wan Huiqing Yin Yurong Xing Hongle Li Jing He Fucheng He |
| author_sort | Chang Wang |
| collection | DOAJ |
| description | Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive. Methods The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Results CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation. Conclusions IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients. |
| first_indexed | 2024-04-12T01:02:35Z |
| format | Article |
| id | doaj.art-a96fecc0c59341a4894b208958e0c569 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-12T01:02:35Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-a96fecc0c59341a4894b208958e0c5692022-12-22T03:54:25ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662022-12-0141111810.1186/s13046-022-02550-8IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axisChang Wang0Mingxia Zhou1Peiyu Zhu2Chenxi Ju3Jinxiu Sheng4Dan Du5Junhu Wan6Huiqing Yin7Yurong Xing8Hongle Li9Jing He10Fucheng He11Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Gastroenterology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou UniversityCenter of Health Examination, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Medical Laboratory, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive. Methods The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Results CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation. Conclusions IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients.https://doi.org/10.1186/s13046-022-02550-8Esophageal squamous cell carcinoma (ESCC)CircRUNX1FOXP3IGF2BP2Biomarker |
| spellingShingle | Chang Wang Mingxia Zhou Peiyu Zhu Chenxi Ju Jinxiu Sheng Dan Du Junhu Wan Huiqing Yin Yurong Xing Hongle Li Jing He Fucheng He IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis Journal of Experimental & Clinical Cancer Research Esophageal squamous cell carcinoma (ESCC) CircRUNX1 FOXP3 IGF2BP2 Biomarker |
| title | IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis |
| title_full | IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis |
| title_fullStr | IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis |
| title_full_unstemmed | IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis |
| title_short | IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis |
| title_sort | igf2bp2 induced circrunx1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through mir 449b 5p foxp3 axis |
| topic | Esophageal squamous cell carcinoma (ESCC) CircRUNX1 FOXP3 IGF2BP2 Biomarker |
| url | https://doi.org/10.1186/s13046-022-02550-8 |
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