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CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play an important role in cancer. However, the mechanisms by which circRNAs regulate gene expression in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study seeks to elucidate the role that circRNAs play in the prolifera...

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Autores principales: Chen, Genwen, Shi, Yanting, Zhang, Yu, Sun, Jianyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722018/
https://www.ncbi.nlm.nih.gov/pubmed/29255366
http://dx.doi.org/10.2147/OTT.S150678
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author Chen, Genwen
Shi, Yanting
Zhang, Yu
Sun, Jianyong
author_facet Chen, Genwen
Shi, Yanting
Zhang, Yu
Sun, Jianyong
author_sort Chen, Genwen
collection PubMed
description Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play an important role in cancer. However, the mechanisms by which circRNAs regulate gene expression in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study seeks to elucidate the role that circRNAs play in the proliferation of PDAC cells. On the basis of previous studies of circRNA expression profiles in PDAC, we found that the circRNA_100782 was markedly upregulated in PDAC tissue. Functional experiments revealed that circRNA_100782 down-regulation inhibited BxPC3 cell proliferation and colony formation. Loss-of-function studies showed that knockdown of circRNA_100782 inhibited cell proliferation by downregulating the microRNA-124 (miR-124) target genes interleukin-6 receptor (IL6R) and signal transducer and activator of transcription 3 (STAT3). Overexpression of miR-124 also inhibited BxPC3 cell proliferation by reducing the expression of IL6R and STAT3, which was consistent with the result of silencing circRNA_100782. In addition, luciferase assay revealed that miR-124 was a direct target of circRNA_100782. Silencing STAT3 inhibited BxPC3 cell proliferation and colony formation. Cell viability was reduced in BxPC3 cells treated with si-circRNA_100782 and miR-124 mimic, and this effect could be attenuated by activating STAT3. In vivo study validated that circRNA_100782 knockdown suppressed BxPC3 xenografts in nude mice. Taken together, these results suggest that circRNA_100782 regulates BxPC3 cell proliferation by acting as miR-124 sponge through the IL6–STAT3 pathway.
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spelling pubmed-57220182017-12-18 CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway Chen, Genwen Shi, Yanting Zhang, Yu Sun, Jianyong Onco Targets Ther Original Research Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play an important role in cancer. However, the mechanisms by which circRNAs regulate gene expression in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study seeks to elucidate the role that circRNAs play in the proliferation of PDAC cells. On the basis of previous studies of circRNA expression profiles in PDAC, we found that the circRNA_100782 was markedly upregulated in PDAC tissue. Functional experiments revealed that circRNA_100782 down-regulation inhibited BxPC3 cell proliferation and colony formation. Loss-of-function studies showed that knockdown of circRNA_100782 inhibited cell proliferation by downregulating the microRNA-124 (miR-124) target genes interleukin-6 receptor (IL6R) and signal transducer and activator of transcription 3 (STAT3). Overexpression of miR-124 also inhibited BxPC3 cell proliferation by reducing the expression of IL6R and STAT3, which was consistent with the result of silencing circRNA_100782. In addition, luciferase assay revealed that miR-124 was a direct target of circRNA_100782. Silencing STAT3 inhibited BxPC3 cell proliferation and colony formation. Cell viability was reduced in BxPC3 cells treated with si-circRNA_100782 and miR-124 mimic, and this effect could be attenuated by activating STAT3. In vivo study validated that circRNA_100782 knockdown suppressed BxPC3 xenografts in nude mice. Taken together, these results suggest that circRNA_100782 regulates BxPC3 cell proliferation by acting as miR-124 sponge through the IL6–STAT3 pathway. Dove Medical Press 2017-12-05 /pmc/articles/PMC5722018/ /pubmed/29255366 http://dx.doi.org/10.2147/OTT.S150678 Text en © 2017 Chen et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Chen, Genwen
Shi, Yanting
Zhang, Yu
Sun, Jianyong
CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway
title CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway
title_full CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway
title_fullStr CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway
title_full_unstemmed CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway
title_short CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway
title_sort circrna_100782 regulates pancreatic carcinoma proliferation through the il6-stat3 pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722018/
https://www.ncbi.nlm.nih.gov/pubmed/29255366
http://dx.doi.org/10.2147/OTT.S150678
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