CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis

Dan Shi,1 Huiyun Li,2 Junge Zhang,3 Yadong Li1 1Department of Oral Medicine Centre, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Anesthesiology, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s...

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Main Authors: Shi D, Li H, Zhang J, Li Y
Format: Article
Language:English
Published: Dove Medical Press 2021-02-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/circgdi2-regulates-the-proliferation-migration-invasion-and-apoptosis--peer-reviewed-article-CMAR
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author Shi D
Li H
Zhang J
Li Y
author_facet Shi D
Li H
Zhang J
Li Y
author_sort Shi D
collection DOAJ
description Dan Shi,1 Huiyun Li,2 Junge Zhang,3 Yadong Li1 1Department of Oral Medicine Centre, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Anesthesiology, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Ophthalmology, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yadong LiDepartment of Oral Medicine Centre, Henan Provincial People’s Hospital, No. 7 Wei-Wu Road, Zhengzhou City, 450000 Henan Province, People’s Republic of ChinaTel +86-186-38723618Email liyadongjibao2009@163.comBackground: Aberrant expression of circular RNA (circRNA) is involved in the occurrence and development of multifarious cancers, including oral squamous cell carcinoma (OSCC). However, the biological role of circGDI2 and the action mechanism in OSCC remain largely unclear.Methods: The expression levels of circGDI2, miR-454-3p and forkhead box F2 (FOXF2) were examined by quantitative real-time PCR (qRT-PCR) or Western blot. The stability of circGDI2 was confirmed by Ribonuclease R (RNase R) assay. Cell Counting Kit 8 (CCK8) assay, colony formation and transwell assay were used to detect cell proliferation, migration or invasion. Cell apoptosis was tested by flow cytometry. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the interaction between miR-454-3p and circGDI2 or FOXF2. Moreover, xenograft mouse models were constructed to assess tumor growth in vivo.Results: CircGDI2 was a stable circRNA and was low expressed in OSCC tissues and cells. CircGDI2 overexpression could effectively inhibit the proliferation, migration, invasion and promote apoptosis in OSCC cells, and suppress OSCC tumor growth in nude mice in vivo. MiR-454-3p could be sponged by circGDI2, and its overexpression could mitigate the suppressive effects of circGDI2 overexpression on OSCC progression. In addition, FOXF2 was a target of miR-454-3p, and miR-454-3p silence could impede the cell growth of OSCC cells by enhancing FOXF2 expression. Meanwhile, circGDI2 positively regulated FOXF2 expression by targeting miR-454-3p.Conclusion: CircGDI2 served as a repressor to restrain OSCC malignancy via miR-454-3p/FOXF2 axis, which might be a novel biomarker for targeted OSCC therapy.Keywords: OSCC, circGDI2, miR-454-3p, FOXF2
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spelling doaj.art-ee41903ad886432aa7f78ea164f0683e2022-12-21T23:01:50ZengDove Medical PressCancer Management and Research1179-13222021-02-01Volume 131371138261990CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 AxisShi DLi HZhang JLi YDan Shi,1 Huiyun Li,2 Junge Zhang,3 Yadong Li1 1Department of Oral Medicine Centre, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 2Department of Anesthesiology, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Ophthalmology, Henan Provincial People’s Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yadong LiDepartment of Oral Medicine Centre, Henan Provincial People’s Hospital, No. 7 Wei-Wu Road, Zhengzhou City, 450000 Henan Province, People’s Republic of ChinaTel +86-186-38723618Email liyadongjibao2009@163.comBackground: Aberrant expression of circular RNA (circRNA) is involved in the occurrence and development of multifarious cancers, including oral squamous cell carcinoma (OSCC). However, the biological role of circGDI2 and the action mechanism in OSCC remain largely unclear.Methods: The expression levels of circGDI2, miR-454-3p and forkhead box F2 (FOXF2) were examined by quantitative real-time PCR (qRT-PCR) or Western blot. The stability of circGDI2 was confirmed by Ribonuclease R (RNase R) assay. Cell Counting Kit 8 (CCK8) assay, colony formation and transwell assay were used to detect cell proliferation, migration or invasion. Cell apoptosis was tested by flow cytometry. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the interaction between miR-454-3p and circGDI2 or FOXF2. Moreover, xenograft mouse models were constructed to assess tumor growth in vivo.Results: CircGDI2 was a stable circRNA and was low expressed in OSCC tissues and cells. CircGDI2 overexpression could effectively inhibit the proliferation, migration, invasion and promote apoptosis in OSCC cells, and suppress OSCC tumor growth in nude mice in vivo. MiR-454-3p could be sponged by circGDI2, and its overexpression could mitigate the suppressive effects of circGDI2 overexpression on OSCC progression. In addition, FOXF2 was a target of miR-454-3p, and miR-454-3p silence could impede the cell growth of OSCC cells by enhancing FOXF2 expression. Meanwhile, circGDI2 positively regulated FOXF2 expression by targeting miR-454-3p.Conclusion: CircGDI2 served as a repressor to restrain OSCC malignancy via miR-454-3p/FOXF2 axis, which might be a novel biomarker for targeted OSCC therapy.Keywords: OSCC, circGDI2, miR-454-3p, FOXF2https://www.dovepress.com/circgdi2-regulates-the-proliferation-migration-invasion-and-apoptosis--peer-reviewed-article-CMARoscccircgdi2mir-454-3pfoxf2
spellingShingle Shi D
Li H
Zhang J
Li Y
CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis
Cancer Management and Research
oscc
circgdi2
mir-454-3p
foxf2
title CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis
title_full CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis
title_fullStr CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis
title_full_unstemmed CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis
title_short CircGDI2 Regulates the Proliferation, Migration, Invasion and Apoptosis of OSCC via miR-454-3p/FOXF2 Axis
title_sort circgdi2 regulates the proliferation migration invasion and apoptosis of oscc via mir 454 3p foxf2 axis
topic oscc
circgdi2
mir-454-3p
foxf2
url https://www.dovepress.com/circgdi2-regulates-the-proliferation-migration-invasion-and-apoptosis--peer-reviewed-article-CMAR
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