Cholangiocarcinoma (CCA) has accounted for a high rate of mortality and morbidity in the recent years. Long non-coding RNAs (lncRNAs) play an important role in different cellular environments, including cancer. As such, they have been used as potential targets during CCA therapy. The objective of this study was to investigate the effects of lncRNA PVT1 on CCA and its mechanisms behind lncRNA PVT1 regulation. The interactions among SOX2, lncRNA PVT1, miR-186 and SEMA4D were verified by chromatin immunoprecipitation, RNA immunoprecipitation and dual luciferase reporter gene assay. Gain- and loss-of-function experiments were conducted to explore the modulatory effects of SOX2, lncRNA PVT1, miR-186 and SEMA4D on cell viability, migration and invasion of CCA by CCK-8 and Transwell assays. In vivo effects of lncRNA PVT1 or SEMA4D were studied in a nude mouse model. MiR-186 was poorly expressed while SOX2, lncRNA PVT1 and SEMA4D were highly expressed in CCA cells. SOX2 induced the transcriptional activation of lncRNA PVT1 expression to promote proliferation, migration and invasion of CCA cells. LncRNA PVT1 bound to miR-186 and miR-186 was found to target SEMA4D. The overexpression of lncRNA PVT1 and SEMA4D, as well as the inhibition of miR-186 led to elevated CCA cell proliferation, migration and invasion. In vivo experiments confirmed the inhibitory role of lncRNA PVT1 knockdown or SEMA4D knockdown in CCA. All in all, SOX2 down-regulated miR-186 through the transcriptional activation of lncRNA PVT1, whereas elevating SEMA4D expression, thus promoting the progression of CCA.
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September 2020
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Cover Image
Thermogenesis of Arum maculatum. The cover of this issue of the Biochemical Journal features an image from Ito et al., who report the temperature-inducible degradation of AOX proteins in mitochondria from appendices of A. maculatum. Image courtesy of Kikukatsu Ito.
Research Article|
September 24 2020
SOX2 knockdown slows cholangiocarcinoma progression through inhibition of transcriptional activation of lncRNA PVT1
Aijun Yu
;
1The First Department of General Surgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, P.R. China
Correspondence: Aijun Yu (yro461@163.com)
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Luwen Zhao;
Luwen Zhao
2The First Department of Gynecology, Affiliated Hospital of Chengde Medical University, Chengde 067000, P.R. China
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Qingmin Kang;
Qingmin Kang
1The First Department of General Surgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, P.R. China
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Jian Li;
Jian Li
1The First Department of General Surgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, P.R. China
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Kai Chen;
Kai Chen
1The First Department of General Surgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, P.R. China
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Hua Fu
Hua Fu
1The First Department of General Surgery, Affiliated Hospital of Chengde Medical University, Chengde 067000, P.R. China
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Publisher: Portland Press Ltd
Received:
March 18 2020
Revision Received:
July 26 2020
Accepted:
August 19 2020
Accepted Manuscript online:
August 19 2020
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2020
Biochem J (2020) 477 (18): 3527–3540.
Article history
Received:
March 18 2020
Revision Received:
July 26 2020
Accepted:
August 19 2020
Accepted Manuscript online:
August 19 2020
Citation
Aijun Yu, Luwen Zhao, Qingmin Kang, Jian Li, Kai Chen, Hua Fu; SOX2 knockdown slows cholangiocarcinoma progression through inhibition of transcriptional activation of lncRNA PVT1. Biochem J 30 September 2020; 477 (18): 3527–3540. doi: https://doi.org/10.1042/BCJ20200219
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