Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer

Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer

Zhenyu Ye,* Zhaobi Zhu,* Jiaming Xie, Zhenyu Feng, Yecheng Li, Xiangrong Xu, Wei Li, Wei Chen Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, People’s Republic of China*These authors contributed equally to this workCorrespondence...

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Autores principales: Ye Z, Zhu Z, Xie J, Feng Z, Li Y, Xu X, Li W, Chen W
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2020
Materias:
pancreatic cancer
hsa_circ_0000069
tumorigenesis
exosomes
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/202d909ccdec45e496e6be6bae07c858
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spelling oai:doaj.org-article:202d909ccdec45e496e6be6bae07c8582021-12-02T13:57:54ZHsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer1178-2013https://doaj.org/article/202d909ccdec45e496e6be6bae07c8582020-12-01T00:00:00Zhttps://www.dovepress.com/hsacirc0000069-knockdown-inhibits-tumorigenesis-and-exosomes-with-down-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zhenyu Ye,* Zhaobi Zhu,* Jiaming Xie, Zhenyu Feng, Yecheng Li, Xiangrong Xu, Wei Li, Wei Chen Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Chen; Wei Li Department of General SurgeryThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu 215004, People’s Republic of ChinaEmail chenwei1971best@126.com; li.wei1@yandex.comBackground: Circular RNAs (circRNAs) play an important role in the tumorigenesis of pancreatic cancer. However, the expression profiles and roles of circRNAs in pancreatic cancer remain largely unknown.Methods: To identify differentially expressed circRNAs (DEcircRNAs) between pancreatic cancer and matched normal tissues, bioinformatics analysis was performed. Hsa_circ_0000069 was identified by 0.bioinformatics analysis. In addition, the level of hsa_circ_0000069 in pancreatic cancer tissues and cell lines, and pancreatic cancer cell-derived exosomes were assessed using RT-qPCR assay.Results: The expression of hsa_circ_0000069 was markedly upregulated in pancreatic cancer tissues and cell lines. SCL/TAL1 interrupting locus (STIL) is the parent gene for hsa_circ_0000069, and its high expression was related to poor overall survival in patients with pancreatic cancer. In addition, downregulation of hsa_circ_0000069 markedly suppressed STIL expression, induced the apoptosis and cell cycle arrest, and inhibited the proliferation, migration and invasion in pancreatic cancer cells. Moreover, hsa_circ_0000069 knockdown inhibited the growth of xenograft pancreatic cancer tumors in vivo. Furthermore, human pancreatic duct epithelial cells (HPDE) are capable of internalizing SW1990 cell-derived exosomes, allowing the transfer of hsa_circ_0000069. Significantly, SW1990 cell-derived exosomes promoted the proliferation, migration and cell cycle progression of HPDE cells, whereas exosomes with downregulated hsa_circ_0000069 suppressed the proliferation, migration and cell cycle progression of HPDE cells, by suppressing STIL expression.Conclusion: Our results suggest that hsa_circ_0000069 knockdown could inhibit pancreatic cancer tumorigenesis and exosomes with downregulated hsa_circ_0000069 could suppress HPDE cell malignant transformation. Collectively, hsa_circ_0000069 might be a therapeutic target for the treatment of pancreatic cancer.Keywords: pancreatic cancer, hsa_circ_0000069, tumorigenesis, exosomesYe ZZhu ZXie JFeng ZLi YXu XLi WChen WDove Medical Pressarticlepancreatic cancerhsa_circ_0000069tumorigenesisexosomesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 9859-9873 (2020)
institution DOAJ
collection DOAJ
language EN
topic pancreatic cancer
hsa_circ_0000069
tumorigenesis
exosomes
Medicine (General)
R5-920
spellingShingle pancreatic cancer
hsa_circ_0000069
tumorigenesis
exosomes
Medicine (General)
R5-920
Ye Z
Zhu Z
Xie J
Feng Z
Li Y
Xu X
Li W
Chen W
Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer
description Zhenyu Ye,* Zhaobi Zhu,* Jiaming Xie, Zhenyu Feng, Yecheng Li, Xiangrong Xu, Wei Li, Wei Chen Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Chen; Wei Li Department of General SurgeryThe Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu 215004, People’s Republic of ChinaEmail chenwei1971best@126.com; li.wei1@yandex.comBackground: Circular RNAs (circRNAs) play an important role in the tumorigenesis of pancreatic cancer. However, the expression profiles and roles of circRNAs in pancreatic cancer remain largely unknown.Methods: To identify differentially expressed circRNAs (DEcircRNAs) between pancreatic cancer and matched normal tissues, bioinformatics analysis was performed. Hsa_circ_0000069 was identified by 0.bioinformatics analysis. In addition, the level of hsa_circ_0000069 in pancreatic cancer tissues and cell lines, and pancreatic cancer cell-derived exosomes were assessed using RT-qPCR assay.Results: The expression of hsa_circ_0000069 was markedly upregulated in pancreatic cancer tissues and cell lines. SCL/TAL1 interrupting locus (STIL) is the parent gene for hsa_circ_0000069, and its high expression was related to poor overall survival in patients with pancreatic cancer. In addition, downregulation of hsa_circ_0000069 markedly suppressed STIL expression, induced the apoptosis and cell cycle arrest, and inhibited the proliferation, migration and invasion in pancreatic cancer cells. Moreover, hsa_circ_0000069 knockdown inhibited the growth of xenograft pancreatic cancer tumors in vivo. Furthermore, human pancreatic duct epithelial cells (HPDE) are capable of internalizing SW1990 cell-derived exosomes, allowing the transfer of hsa_circ_0000069. Significantly, SW1990 cell-derived exosomes promoted the proliferation, migration and cell cycle progression of HPDE cells, whereas exosomes with downregulated hsa_circ_0000069 suppressed the proliferation, migration and cell cycle progression of HPDE cells, by suppressing STIL expression.Conclusion: Our results suggest that hsa_circ_0000069 knockdown could inhibit pancreatic cancer tumorigenesis and exosomes with downregulated hsa_circ_0000069 could suppress HPDE cell malignant transformation. Collectively, hsa_circ_0000069 might be a therapeutic target for the treatment of pancreatic cancer.Keywords: pancreatic cancer, hsa_circ_0000069, tumorigenesis, exosomes
format article
author Ye Z
Zhu Z
Xie J
Feng Z
Li Y
Xu X
Li W
Chen W
author_facet Ye Z
Zhu Z
Xie J
Feng Z
Li Y
Xu X
Li W
Chen W
author_sort Ye Z
title Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer
title_short Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer
title_full Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer
title_fullStr Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer
title_full_unstemmed Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer
title_sort hsa_circ_0000069 knockdown inhibits tumorigenesis and exosomes with downregulated hsa_circ_0000069 suppress malignant transformation via inhibition of stil in pancreatic cancer
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/202d909ccdec45e496e6be6bae07c858
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