MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway
Shuai Wang, Shanshan Du, Yong Lv, Fengyan Zhang, Wenzhan WangDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of ChinaPurpose: Previous studies have revealed that microRNA-665 (miR-665) is dysregulated in a varie...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-04-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/microrna-665-inhibits-the-oncogenicity-of-retinoblastoma-by-directly-t-peer-reviewed-article-CMAR |
| _version_ | 1818272165578932224 |
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| author | Wang S Du S Lv Y Zhang F Wang W |
| author_facet | Wang S Du S Lv Y Zhang F Wang W |
| author_sort | Wang S |
| collection | DOAJ |
| description | Shuai Wang, Shanshan Du, Yong Lv, Fengyan Zhang, Wenzhan WangDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of ChinaPurpose: Previous studies have revealed that microRNA-665 (miR-665) is dysregulated in a variety of human cancers. However, little is known regarding its expression profiles and functions in retinoblastoma (RB). Therefore, the aims of our study were to evaluate miR-665 expression in RB and determine the precise roles of miR-665 in the progression of RB.Patients and methods: Herein, RT-qPCR was used to determine miR-665 expression levels in RB tissues and cell lines, and a series of functional experiments were performed to explore the influence of miR-665 on RB cell proliferation, colony formation, apoptosis, migration, and invasion as well as tumor growth. The molecular mechanisms underlying the tumor-suppressive action of miR-665 in RB were also explored.Results: We found that miR-665 was markedly reduced in RB tissues and cell lines and that lower miR-665 expression was strongly associated with tumor size, TNM stage, and differentiation in patients with RB. Exogenous expression of miR-665 suppressed cell proliferation, colony formation, migration, and invasion, and induced cell apoptosis in RB cells, while silencing miR-665 expression had the opposite effects. In addition, upregulation of miR-665 decreased the tumor growth of RB cells in vivo. High-mobility group box 1 (HMGB1) was identified as a direct target of miR-665 in RB cells, and decreasing the expression of HMGB1 simulated the regulatory effects of miR-665 overexpression in RB cells, while knockdown of HMGB1 expression counteracted the miR-665-mediated antitumor effects in RB cells. Moreover, miR-665 was shown to regulate the Wnt/β-catenin signaling pathway by targeting HMGB1 in vitro and in vivo.Conclusion: Taken together, our in vitro and in vivo results suggest that miR-665 acts as a tumor-suppressive miRNA in RB by directly targeting HMGB1 and inactivating the Wnt/β-catenin pathway. Hence, this miRNA is a candidate prognostic biomarker and therapeutic target in patients with RB.Keywords: microRNA-665, retinoblastoma, high-mobility group box 1, Wnt/β-catenin pathway, oncogenicity |
| first_indexed | 2024-12-12T21:37:44Z |
| format | Article |
| id | doaj.art-134a030c9b91484c806a11f382e2f6d7 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-12T21:37:44Z |
| publishDate | 2019-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-134a030c9b91484c806a11f382e2f6d72022-12-22T00:11:08ZengDove Medical PressCancer Management and Research1179-13222019-04-01Volume 113111312345094MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathwayWang SDu SLv YZhang FWang WShuai Wang, Shanshan Du, Yong Lv, Fengyan Zhang, Wenzhan WangDepartment of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, People’s Republic of ChinaPurpose: Previous studies have revealed that microRNA-665 (miR-665) is dysregulated in a variety of human cancers. However, little is known regarding its expression profiles and functions in retinoblastoma (RB). Therefore, the aims of our study were to evaluate miR-665 expression in RB and determine the precise roles of miR-665 in the progression of RB.Patients and methods: Herein, RT-qPCR was used to determine miR-665 expression levels in RB tissues and cell lines, and a series of functional experiments were performed to explore the influence of miR-665 on RB cell proliferation, colony formation, apoptosis, migration, and invasion as well as tumor growth. The molecular mechanisms underlying the tumor-suppressive action of miR-665 in RB were also explored.Results: We found that miR-665 was markedly reduced in RB tissues and cell lines and that lower miR-665 expression was strongly associated with tumor size, TNM stage, and differentiation in patients with RB. Exogenous expression of miR-665 suppressed cell proliferation, colony formation, migration, and invasion, and induced cell apoptosis in RB cells, while silencing miR-665 expression had the opposite effects. In addition, upregulation of miR-665 decreased the tumor growth of RB cells in vivo. High-mobility group box 1 (HMGB1) was identified as a direct target of miR-665 in RB cells, and decreasing the expression of HMGB1 simulated the regulatory effects of miR-665 overexpression in RB cells, while knockdown of HMGB1 expression counteracted the miR-665-mediated antitumor effects in RB cells. Moreover, miR-665 was shown to regulate the Wnt/β-catenin signaling pathway by targeting HMGB1 in vitro and in vivo.Conclusion: Taken together, our in vitro and in vivo results suggest that miR-665 acts as a tumor-suppressive miRNA in RB by directly targeting HMGB1 and inactivating the Wnt/β-catenin pathway. Hence, this miRNA is a candidate prognostic biomarker and therapeutic target in patients with RB.Keywords: microRNA-665, retinoblastoma, high-mobility group box 1, Wnt/β-catenin pathway, oncogenicityhttps://www.dovepress.com/microrna-665-inhibits-the-oncogenicity-of-retinoblastoma-by-directly-t-peer-reviewed-article-CMARmicroRNA-665retinoblastomahigh-mobility group box 1Wnt/β-catenin pathwayoncogenicity |
| spellingShingle | Wang S Du S Lv Y Zhang F Wang W MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway Cancer Management and Research microRNA-665 retinoblastoma high-mobility group box 1 Wnt/β-catenin pathway oncogenicity |
| title | MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway |
| title_full | MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway |
| title_fullStr | MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway |
| title_full_unstemmed | MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway |
| title_short | MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway |
| title_sort | microrna 665 inhibits the oncogenicity of retinoblastoma by directly targeting high mobility group box 1 and inactivating the wnt beta catenin pathway |
| topic | microRNA-665 retinoblastoma high-mobility group box 1 Wnt/β-catenin pathway oncogenicity |
| url | https://www.dovepress.com/microrna-665-inhibits-the-oncogenicity-of-retinoblastoma-by-directly-t-peer-reviewed-article-CMAR |
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