Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer
| العنوان: | Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer |
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| المؤلفون: | Hanno Nieß, Joachim W. Ellwart, Josef Mysliwietz, Karl-Walter Jauch, Ivan Ischenko, L. Zhao, B. Schwarz, Peter J. Nelson, Peter Camaj, Qi Bao, Yan Wang, Yue Zhao, Andrea Renner, Christiane Bruns |
| المصدر: | Targeted Oncology. 10:535-548 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Cancer Research, Carcinogenesis, Cellular differentiation, Mice, Nude, Biology, Transfection, medicine.disease_cause, Mice, chemistry.chemical_compound, Side population, Cell Line, Tumor, Pancreatic cancer, medicine, Animals, Humans, Pharmacology (medical), Antagomir, Neoplasm Metastasis, Cell Proliferation, Mice, Inbred BALB C, Cell growth, Cell Differentiation, Oligonucleotides, Antisense, medicine.disease, Xenograft Model Antitumor Assays, Molecular biology, Up-Regulation, Pancreatic Neoplasms, MicroRNAs, Oncology, chemistry, Drug Resistance, Neoplasm, Tumor progression, Neoplastic Stem Cells |
| الوصف: | Our preliminary studies identified a small population side population (SP) cells in pancreatic cancer cells with stem cell-like properties, which were able to induce fast and aggressive tumor formation in nude mice. Gene expression analysis showed a significant difference in the expression of more than 1,300 genes in SP cells, among which a highly significant difference in microRNA expression of miR-21 and miR-221 between SP and NSP cells was identified. SP cells were identified and characterized by flow cytometry using Hoechst 33342 dye staining from a highly metastatic human pancreatic cancer cell line (L3.6pl). Antagomir transfection was performed using miRNA-21 and miRNA-221 antisense oligonucleotides (ASOs) and followed by detection of cell apoptosis, cell cycle progression, chemosensitivity, and invasion. Sorted SP cells from gemcitabine-resistant L3.6pl cells (L3.6pl(Gres)-SP) cells were orthotopically implanted in nude mice with or without miRNA-21 and miRNA-221 ASOs mono- and combination therapy. The administration of antagomir-21 and antagomir-221 significantly reduced the SP cell fraction, decreased SP cell differentiation, and downstream gene regulation, and thereby induced reduction of L3.6pl cell proliferation, invasion, and chemoresistance against gemcitabine and 5-Fluorouracil. Combination of ASOs therapy against miRNA-21 and miRNA-221 significantly inhibited primary tumor growth and metastasis compared to single antagomir treatment, especially, in L3.6plGres-SP-induced pancreatic tumor growth in vivo. These findings further indicate that the inhibition of miR-21 and miR-221 appear particularly suitable to target stem-like subpopulations and address their specific biological function to promote tumor progression in pancreatic cancer. |
| تدمد: | 1776-260X 1776-2596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f40286b03885c5635aa3ebebf052c1aaTest https://doi.org/10.1007/s11523-015-0360-2Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....f40286b03885c5635aa3ebebf052c1aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1776260X 17762596 |
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