dc.contributor.author | Ji, Qing | |
dc.contributor.author | Hao, Xinbao | |
dc.contributor.author | Zhang, Min | |
dc.contributor.author | Tang, Wenhua | |
dc.contributor.author | Yang, Meng | |
dc.contributor.author | Li, Ling | |
dc.contributor.author | Xiang, Debing | |
dc.contributor.author | DeSano, Jeffrey | |
dc.contributor.author | Bommer, Guido | |
dc.contributor.author | Fan, Daiming | |
dc.contributor.author | Fearon, Eric R. | |
dc.contributor.author | Lawrence, Theodore S. | |
dc.contributor.author | Xu, Liang | |
dc.date.accessioned | 2015-04-09T16:26:15Z | |
dc.date.available | 2015-04-09T16:26:15Z | |
dc.date.issued | 2009-08-28 | |
dc.identifier.citation | Ji Q, Hao X, Zhang M, Tang W, Yang M, et al. (2009) MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells. PLoS ONE 4(8): e6816. http://dx.doi.org/10.1371/journal.pone.0006816. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17360 | |
dc.description | This is the published version, also available here: http://dx.doi.org/10.1371/journal.pone.0006816. | en_US |
dc.description.abstract | BackgroundMicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. Among the target proteins regulated by miR-34 are Notch pathway proteins and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells.
Methodology/Principal FindingsWe examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines MiaPaCa2 and BxPC3, and the potential link to pancreatic cancer stem cells. Restoration of miR-34 expression in the pancreatic cancer cells by either transfection of miR-34 mimics or infection with lentiviral miR-34-MIF downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cells to chemotherapy and radiation. We identified that CD44+/CD133+ MiaPaCa2 cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor formation in vivo.
Conclusions/SignificanceOur results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53–miR34, potentially via inhibiting pancreatic cancer stem cells. | en_US |
dc.publisher | Public Library of Science | en_US |
dc.subject | Cancer Stem Cells | en_US |
dc.subject | Pancreatic cancer | en_US |
dc.subject | Gene Targeting | en_US |
dc.subject | MicroRNAs | en_US |
dc.subject | Stem Cells | en_US |
dc.subject | Gene Expression | en_US |
dc.subject | Tumor Stem Cells | en_US |
dc.subject | Stem Cell Therapy | en_US |
dc.title | MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells | en_US |
dc.type | Article | |
kusw.kuauthor | Xu, Liang | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1371/journal.pone.0006816 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess | |