MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway
Abstract Background Current evidence indicates that miR-608 is widely down-regulated in various malignant tumors including liver cancer, colon cancer, lung cancer and glioma, and acts as a tumor suppressor by inhibiting cell proliferation, invasion and migration or by promoting apoptosis. The specif...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-05-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12943-017-0664-1 |
| _version_ | 1818428517859196928 |
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| author | Zhen Liang Xiao Wang Xin Xu Bo Xie Alin Ji Shuai Meng Shiqi Li Yi Zhu Jian Wu Zhenghui Hu Yiwei Lin Xiangyi Zheng Liping Xie Ben Liu |
| author_facet | Zhen Liang Xiao Wang Xin Xu Bo Xie Alin Ji Shuai Meng Shiqi Li Yi Zhu Jian Wu Zhenghui Hu Yiwei Lin Xiangyi Zheng Liping Xie Ben Liu |
| author_sort | Zhen Liang |
| collection | DOAJ |
| description | Abstract Background Current evidence indicates that miR-608 is widely down-regulated in various malignant tumors including liver cancer, colon cancer, lung cancer and glioma, and acts as a tumor suppressor by inhibiting cell proliferation, invasion and migration or by promoting apoptosis. The specific biological function of miR-608 in bladder cancer is still unknown. Methods qRT-PCR and Chromogenic in Situ Hybridization (CISH) was conducted to assess the expression of miR-608 in paired BCa tissues and adjacent non-tumor bladder urothelial tissues. Bisulfite sequencing PCR was used for DNA methylation analysis. CCK-8, colony formation and flow cytometry assays were performed, and a xenograft model was studied. Immunohistochemistry staining was performed with peroxidase and DAB. The target of miR-608 was validated with a dual-luciferase reporter assay, quantitative RT-PCR, and Western blotting. Results miR-608 is frequently down-regulated in human BCa tissues. The methylation status of CpG islands is involved in the regulation of miR-608 expression. Overexpression of miR-608 inhibits the proliferation and tumorigenesis of BCa cells in vitro and in vivo. Additionally, up-regulation of miR-608 in BCa cells induces G1-phase arrest through AKT/FOXO3a signaling. In contrast, down-regulation of miR-608 promotes proliferation and cell cycle progression in BCa cells. Moreover, the expression of FLOT1 was directly inhibited by miR-608, the down-regulation of FLOT1 induced by siFLOT1 could be significantly reversed by miR-608 inhibitor. Similarly, the up-regulation of FLOT1 by FLOT1 overexpression plasmid (pFLOT1) could also reverse the suppressed cell proliferation caused by miR-608. Conclusions miR-608 is a potential tumor suppressor in BCa, and the restoration of miR-608 might be a promising therapeutic option for BCa. |
| first_indexed | 2024-12-14T15:02:53Z |
| format | Article |
| id | doaj.art-7a996bb10bbc4e57bc93885b1cc4f072 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-14T15:02:53Z |
| publishDate | 2017-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-7a996bb10bbc4e57bc93885b1cc4f0722022-12-21T22:56:47ZengBMCMolecular Cancer1476-45982017-05-0116111310.1186/s12943-017-0664-1MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathwayZhen Liang0Xiao Wang1Xin Xu2Bo Xie3Alin Ji4Shuai Meng5Shiqi Li6Yi Zhu7Jian Wu8Zhenghui Hu9Yiwei Lin10Xiangyi Zheng11Liping Xie12Ben Liu13Department of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, TongDe Hospital of Zhejiang ProvinceDepartment of Urology, Zhejiang Provincial People’s HospitalDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineDepartment of Urology, the First Affiliated Hospital, Zhejiang University, School of MedicineAbstract Background Current evidence indicates that miR-608 is widely down-regulated in various malignant tumors including liver cancer, colon cancer, lung cancer and glioma, and acts as a tumor suppressor by inhibiting cell proliferation, invasion and migration or by promoting apoptosis. The specific biological function of miR-608 in bladder cancer is still unknown. Methods qRT-PCR and Chromogenic in Situ Hybridization (CISH) was conducted to assess the expression of miR-608 in paired BCa tissues and adjacent non-tumor bladder urothelial tissues. Bisulfite sequencing PCR was used for DNA methylation analysis. CCK-8, colony formation and flow cytometry assays were performed, and a xenograft model was studied. Immunohistochemistry staining was performed with peroxidase and DAB. The target of miR-608 was validated with a dual-luciferase reporter assay, quantitative RT-PCR, and Western blotting. Results miR-608 is frequently down-regulated in human BCa tissues. The methylation status of CpG islands is involved in the regulation of miR-608 expression. Overexpression of miR-608 inhibits the proliferation and tumorigenesis of BCa cells in vitro and in vivo. Additionally, up-regulation of miR-608 in BCa cells induces G1-phase arrest through AKT/FOXO3a signaling. In contrast, down-regulation of miR-608 promotes proliferation and cell cycle progression in BCa cells. Moreover, the expression of FLOT1 was directly inhibited by miR-608, the down-regulation of FLOT1 induced by siFLOT1 could be significantly reversed by miR-608 inhibitor. Similarly, the up-regulation of FLOT1 by FLOT1 overexpression plasmid (pFLOT1) could also reverse the suppressed cell proliferation caused by miR-608. Conclusions miR-608 is a potential tumor suppressor in BCa, and the restoration of miR-608 might be a promising therapeutic option for BCa.http://link.springer.com/article/10.1186/s12943-017-0664-1Bladder cancerProliferationMicroRNA-608FLOT1 |
| spellingShingle | Zhen Liang Xiao Wang Xin Xu Bo Xie Alin Ji Shuai Meng Shiqi Li Yi Zhu Jian Wu Zhenghui Hu Yiwei Lin Xiangyi Zheng Liping Xie Ben Liu MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway Molecular Cancer Bladder cancer Proliferation MicroRNA-608 FLOT1 |
| title | MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway |
| title_full | MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway |
| title_fullStr | MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway |
| title_full_unstemmed | MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway |
| title_short | MicroRNA-608 inhibits proliferation of bladder cancer via AKT/FOXO3a signaling pathway |
| title_sort | microrna 608 inhibits proliferation of bladder cancer via akt foxo3a signaling pathway |
| topic | Bladder cancer Proliferation MicroRNA-608 FLOT1 |
| url | http://link.springer.com/article/10.1186/s12943-017-0664-1 |
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