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CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling

BACKGROUND: Circular RNAs (CircRNAs) have been recently implicated in the progression of pancreatic cancer (PC). AIMS: To investigate the involvement of CircCCT3 in PC and studying its interactions and functioning during the progression of PC in vitro and in vivo, using methods of molecular biology...

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Autores principales: Hou, Ji-Ping, Men, Xue-Bo, Yang, Lian-Ying, Han, En-Kun, Han, Chun-Qi, Liu, Li-Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Trakya University School of Medicine 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880967/
https://www.ncbi.nlm.nih.gov/pubmed/34274912
http://dx.doi.org/10.5152/balkanmedj.2021.21145
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author Hou, Ji-Ping
Men, Xue-Bo
Yang, Lian-Ying
Han, En-Kun
Han, Chun-Qi
Liu, Li-Bin
author_facet Hou, Ji-Ping
Men, Xue-Bo
Yang, Lian-Ying
Han, En-Kun
Han, Chun-Qi
Liu, Li-Bin
author_sort Hou, Ji-Ping
collection PubMed
description BACKGROUND: Circular RNAs (CircRNAs) have been recently implicated in the progression of pancreatic cancer (PC). AIMS: To investigate the involvement of CircCCT3 in PC and studying its interactions and functioning during the progression of PC in vitro and in vivo, using methods of molecular biology and bioinformatics. STUDY DESIG: n: Experimental study. METHODS: The expressions of CircCCT3 and miR-613 in pancreatic ­carcinoma tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction (PCR). The relationship between clinical pathologic features as well as the survival rate and CircCCT3 expression was analyzed with chi-square test and the Kaplan–Meier method. CCK-8, wound healing, transwell assays, and the fluorescein isothiocyanate-AnnexinV/propidium iodide (FITC-AnnexinV/PI) assay were used to assess cell proliferation, migration, invasion, and apoptosis after CircCCT3 overexpression or downregulation. The Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to validate the potential interaction of CircCCT3, miR-613, and vascular endothelial growth factor (VEGFA). The nude mouse xenograft tumor assay was used to detect CircCCT3 effects on pancreatic tumorigenesis in vivo. Western blotting analysis was performed to examine the VEGFA and the vascular endothelial growth factor receptor 2 (VEGFR2) protein expressions following. RESULTS: CircCCT3 expression was significantly increased in PC tissues (3.41 ± 0.57 vs. 1.00 ± 0.10, P < .01) and cell lines (Patu8988 2.57 ± 0.20; SW1990 2.88 ± 0.10; BxPC-3 2.45 ± 0.20; Panc02 2.99 ± 0.10 vs. H6c7 1.00 ± 0.10; all P < .001). CircCCT3 expression was negatively correlated with miR-613 expression. PC patients with high CircCCT3 expression exhibited significantly poorer overall survival rate than those patients with low CircCCT3 expression (P = .013). Moreover, it was found that CircCCT3 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis in PC cells. The CircCCT3 acted as a sponge for the miR-613 to facilitate VEGFA and VEGFR2 expression. si-CirCCT3 also inhibited tumor growth of PC in nude mice. si-CircCCT3 reduced VEGFA and VEGFR2 expression, whereas overexpression of CircCCT3 increased VEGFA and VEGFR2 expression. CONCLUSION: Increased CircCCT3 suggests a poor prognosis for PC patients and promotes the migration and invasion through targeting VEGFA/VEGFR2 signaling. CircCCT3 may serve as a potential and promising therapeutic target for PC treatment.
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spelling pubmed-88809672022-03-10 CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling Hou, Ji-Ping Men, Xue-Bo Yang, Lian-Ying Han, En-Kun Han, Chun-Qi Liu, Li-Bin Balkan Med J Original Article BACKGROUND: Circular RNAs (CircRNAs) have been recently implicated in the progression of pancreatic cancer (PC). AIMS: To investigate the involvement of CircCCT3 in PC and studying its interactions and functioning during the progression of PC in vitro and in vivo, using methods of molecular biology and bioinformatics. STUDY DESIG: n: Experimental study. METHODS: The expressions of CircCCT3 and miR-613 in pancreatic ­carcinoma tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction (PCR). The relationship between clinical pathologic features as well as the survival rate and CircCCT3 expression was analyzed with chi-square test and the Kaplan–Meier method. CCK-8, wound healing, transwell assays, and the fluorescein isothiocyanate-AnnexinV/propidium iodide (FITC-AnnexinV/PI) assay were used to assess cell proliferation, migration, invasion, and apoptosis after CircCCT3 overexpression or downregulation. The Dual-Luciferase reporter assay, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to validate the potential interaction of CircCCT3, miR-613, and vascular endothelial growth factor (VEGFA). The nude mouse xenograft tumor assay was used to detect CircCCT3 effects on pancreatic tumorigenesis in vivo. Western blotting analysis was performed to examine the VEGFA and the vascular endothelial growth factor receptor 2 (VEGFR2) protein expressions following. RESULTS: CircCCT3 expression was significantly increased in PC tissues (3.41 ± 0.57 vs. 1.00 ± 0.10, P < .01) and cell lines (Patu8988 2.57 ± 0.20; SW1990 2.88 ± 0.10; BxPC-3 2.45 ± 0.20; Panc02 2.99 ± 0.10 vs. H6c7 1.00 ± 0.10; all P < .001). CircCCT3 expression was negatively correlated with miR-613 expression. PC patients with high CircCCT3 expression exhibited significantly poorer overall survival rate than those patients with low CircCCT3 expression (P = .013). Moreover, it was found that CircCCT3 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis in PC cells. The CircCCT3 acted as a sponge for the miR-613 to facilitate VEGFA and VEGFR2 expression. si-CirCCT3 also inhibited tumor growth of PC in nude mice. si-CircCCT3 reduced VEGFA and VEGFR2 expression, whereas overexpression of CircCCT3 increased VEGFA and VEGFR2 expression. CONCLUSION: Increased CircCCT3 suggests a poor prognosis for PC patients and promotes the migration and invasion through targeting VEGFA/VEGFR2 signaling. CircCCT3 may serve as a potential and promising therapeutic target for PC treatment. Trakya University School of Medicine 2021-07-01 /pmc/articles/PMC8880967/ /pubmed/34274912 http://dx.doi.org/10.5152/balkanmedj.2021.21145 Text en © Copyright 2021 authors https://creativecommons.org/licenses/by-nc-nd/4.0/ Content of this journal is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Article
Hou, Ji-Ping
Men, Xue-Bo
Yang, Lian-Ying
Han, En-Kun
Han, Chun-Qi
Liu, Li-Bin
CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling
title CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling
title_full CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling
title_fullStr CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling
title_full_unstemmed CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling
title_short CircCCT3 Acts as a Sponge of miR-613 to Promote Tumor Growth of Pancreatic Cancer Through Regulating VEGFA/VEGFR2 Signaling
title_sort circcct3 acts as a sponge of mir-613 to promote tumor growth of pancreatic cancer through regulating vegfa/vegfr2 signaling
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880967/
https://www.ncbi.nlm.nih.gov/pubmed/34274912
http://dx.doi.org/10.5152/balkanmedj.2021.21145
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