FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo
Abstract Backgrounds A number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We...
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-019-6028-z |
| _version_ | 1828530206159142912 |
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| author | Haoran Lu Baofu Yao Xinyuan Wen Baoqing Jia |
| author_facet | Haoran Lu Baofu Yao Xinyuan Wen Baoqing Jia |
| author_sort | Haoran Lu |
| collection | DOAJ |
| description | Abstract Backgrounds A number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We aimed to investigate the effect and mechanisms of circ-FBXW7 on CRC progression. Methods The expression of circ-FBXW7 in CRC patients was detected by PCR. Stably knockdown of circ-FBXW7 (si circ-FBXW7) cell lines and overexpression of circ-FBXW7 (oe circ-FBXW7) cell lines were constructed by small interfering RNA method and plasmids transfection in CRC SW480 and SW620 cells. The functional experiments including cell proliferation, migration and invasion were carried out by cell counting kit-8 (CCK-8) assay, wound healing assay and trans well assay. The xenograft animal models were established to evaluate the effect and the underlying molecular mechanisms of circ-FBXW7 on CRC progression. Results CRC samples had a significantly lower level of circ-FBXW7 compared to normal tissue. si circ-FBXW7 notably promoted the proliferation, colony formation, cell migration and invasion of CRC cell in vitro. On contrast, circ-FBXW7 overexpressed significantly suppressed CRC cell proliferation, migration and invasion. Similarly, si circ-FBXW7 stimulated the tumor growth and circ-FBXW7 overexpression repressed the tumor progression in SW480 and SW620 tumor models, which suggested that circ-FBXW7 could serve as a target biomarker of CRC. Further study found that si circ-FBXW7 up-regulated the mRNA and protein expressions of NEK2 and mTOR, and diminished the PTEN expression. Whereas, overexpressed circ-FBXW7 induced the tumor suppression via reversing the expressions of NEK2, mTOR, and PTEN. Conclusion circ-FBXW7 plays a major role in controlling the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and may be a potential therapeutic target for CRC treatment. Graphical abstract Circ-FBXW7 controls the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and its overexpression inhibits colorectal cancer cell migration and invasion, suggesting the potential therapeutic target for CRC treatment. |
| first_indexed | 2024-12-11T22:19:51Z |
| format | Article |
| id | doaj.art-9a69ed975d4e429eb76d7f10e6292b05 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-11T22:19:51Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-9a69ed975d4e429eb76d7f10e6292b052022-12-22T00:48:29ZengBMCBMC Cancer1471-24072019-09-011911810.1186/s12885-019-6028-zFBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivoHaoran Lu0Baofu Yao1Xinyuan Wen2Baoqing Jia3Department of General Surgery, Chinese PLA General HospitalDepartment of Oncological Surgery, Beijing Geriatric HospitalDepartment of General Surgery, Affiliated Hospital of Jining Medical UniversityDepartment of General Surgery, Chinese PLA General HospitalAbstract Backgrounds A number of circular RNAs (circRNAs) have been identified in various cancer including F-box and WD repeat domain containing 7 (FBXW7) circular RNA (circ-FBXW7), which can suppress glioma cell growth. However, the role of circ-FBXW7 in colorectal cancer (CRC) remains unclear. We aimed to investigate the effect and mechanisms of circ-FBXW7 on CRC progression. Methods The expression of circ-FBXW7 in CRC patients was detected by PCR. Stably knockdown of circ-FBXW7 (si circ-FBXW7) cell lines and overexpression of circ-FBXW7 (oe circ-FBXW7) cell lines were constructed by small interfering RNA method and plasmids transfection in CRC SW480 and SW620 cells. The functional experiments including cell proliferation, migration and invasion were carried out by cell counting kit-8 (CCK-8) assay, wound healing assay and trans well assay. The xenograft animal models were established to evaluate the effect and the underlying molecular mechanisms of circ-FBXW7 on CRC progression. Results CRC samples had a significantly lower level of circ-FBXW7 compared to normal tissue. si circ-FBXW7 notably promoted the proliferation, colony formation, cell migration and invasion of CRC cell in vitro. On contrast, circ-FBXW7 overexpressed significantly suppressed CRC cell proliferation, migration and invasion. Similarly, si circ-FBXW7 stimulated the tumor growth and circ-FBXW7 overexpression repressed the tumor progression in SW480 and SW620 tumor models, which suggested that circ-FBXW7 could serve as a target biomarker of CRC. Further study found that si circ-FBXW7 up-regulated the mRNA and protein expressions of NEK2 and mTOR, and diminished the PTEN expression. Whereas, overexpressed circ-FBXW7 induced the tumor suppression via reversing the expressions of NEK2, mTOR, and PTEN. Conclusion circ-FBXW7 plays a major role in controlling the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and may be a potential therapeutic target for CRC treatment. Graphical abstract Circ-FBXW7 controls the progression of CRC through NEK2, mTOR, and PTEN signaling pathways and its overexpression inhibits colorectal cancer cell migration and invasion, suggesting the potential therapeutic target for CRC treatment.http://link.springer.com/article/10.1186/s12885-019-6028-zColorectal cancercircRNAsCirc-FBXW7Cell proliferationMigrationInvasion |
| spellingShingle | Haoran Lu Baofu Yao Xinyuan Wen Baoqing Jia FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo BMC Cancer Colorectal cancer circRNAs Circ-FBXW7 Cell proliferation Migration Invasion |
| title | FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo |
| title_full | FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo |
| title_fullStr | FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo |
| title_full_unstemmed | FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo |
| title_short | FBXW7 circular RNA regulates proliferation, migration and invasion of colorectal carcinoma through NEK2, mTOR, and PTEN signaling pathways in vitro and in vivo |
| title_sort | fbxw7 circular rna regulates proliferation migration and invasion of colorectal carcinoma through nek2 mtor and pten signaling pathways in vitro and in vivo |
| topic | Colorectal cancer circRNAs Circ-FBXW7 Cell proliferation Migration Invasion |
| url | http://link.springer.com/article/10.1186/s12885-019-6028-z |
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