Hsa_circ_0000069 Knockdown Inhibits Tumorigenesis and Exosomes with Downregulated hsa_circ_0000069 Suppress Malignant Transformation via Inhibition of STIL in Pancreatic Cancer
| Autor: | Zhenyu Feng, Jiaming Xie, Wei Li, Zhenyu Ye, Xiangrong Xu, Yecheng Li, Wei Chen, Zhaobi Zhu |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cell cycle checkpoint
Carcinogenesis Cell pancreatic cancer Biophysics Pharmaceutical Science Bioengineering Apoptosis 02 engineering and technology exosomes 010402 general chemistry medicine.disease_cause 01 natural sciences Malignant transformation Biomaterials Downregulation and upregulation International Journal of Nanomedicine Pancreatic cancer Cell Line Tumor Drug Discovery medicine Humans Original Research Cell Proliferation Gene knockdown Chemistry Organic Chemistry hsa_circ_0000069 Intracellular Signaling Peptides and Proteins General Medicine Cell Cycle Checkpoints RNA Circular 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Gene Expression Regulation Neoplastic Pancreatic Neoplasms tumorigenesis medicine.anatomical_structure Cell Transformation Neoplastic Gene Knockdown Techniques Cancer research 0210 nano-technology |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 1176-9114 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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