| Title |
Antisense inhibition of microRNA-21 and microRNA-221 in tumor-initiating stem-like cells modulates tumorigenesis, metastasis, and chemotherapy resistance in pancreatic cancer
|
|---|---|
| Published in |
Targeted Oncology, February 2015
|
| DOI | 10.1007/s11523-015-0360-2 |
| Pubmed ID | |
| Authors |
Yue Zhao, Lu Zhao, Ivan Ischenko, Qi Bao, Bettina Schwarz, Hanno Nieß, Yan Wang, Andrea Renner, Josef Mysliwietz, Karl-Walter Jauch, Peter J. Nelson, Joachim W. Ellwart, Christiane J. Bruns, Peter Camaj |
| Abstract |
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 (L3.6plGres-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. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 2 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Science communicators (journalists, bloggers, editors) | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 47 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 23% |
| Student > Bachelor | 10 | 21% |
| Researcher | 5 | 11% |
| Student > Master | 3 | 6% |
| Student > Doctoral Student | 2 | 4% |
| Other | 4 | 9% |
| Unknown | 12 | 26% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 23% |
| Medicine and Dentistry | 8 | 17% |
| Agricultural and Biological Sciences | 5 | 11% |
| Chemistry | 4 | 9% |
| Immunology and Microbiology | 2 | 4% |
| Other | 2 | 4% |
| Unknown | 15 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 February 2015.
All research outputs
#17,743,050
of 22,785,242 outputs
Outputs from Targeted Oncology
#319
of 551 outputs
Outputs of similar age
#242,239
of 352,352 outputs
Outputs of similar age from Targeted Oncology
#4
of 7 outputs
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