Show simple item record

dc.contributor.authorJi, Qing
dc.contributor.authorHao, Xinbao
dc.contributor.authorZhang, Min
dc.contributor.authorTang, Wenhua
dc.contributor.authorYang, Meng
dc.contributor.authorLi, Ling
dc.contributor.authorXiang, Debing
dc.contributor.authorDeSano, Jeffrey
dc.contributor.authorBommer, Guido
dc.contributor.authorFan, Daiming
dc.contributor.authorFearon, Eric R.
dc.contributor.authorLawrence, Theodore S.
dc.contributor.authorXu, Liang
dc.identifier.citationJi 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.
dc.descriptionThis is the published version, also available here:

MicroRNAs (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 Findings

We 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/Significance

Our 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.
dc.publisherPublic Library of Scienceen_US
dc.subjectCancer Stem Cellsen_US
dc.subjectPancreatic canceren_US
dc.subjectGene Targetingen_US
dc.subjectStem Cellsen_US
dc.subjectGene Expressionen_US
dc.subjectTumor Stem Cellsen_US
dc.subjectStem Cell Therapyen_US
dc.titleMicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cellsen_US
kusw.kuauthorXu, Liang
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.

Files in this item


This item appears in the following Collection(s)

Show simple item record