Journal article
miR-204 mediated loss of Myeloid cell leukemia-1 results in pancreatic cancer cell death
Molecular cancer, Vol.12(1), pp.105-105
09/11/2013
DOI: 10.1186/1476-4598-12-105
PMCID: PMC3848798
PMID: 24025188
Abstract
Background: Pancreatic cancer is one of the most lethal human malignancies, with an all-stage 5-year survival of <5%, mainly due to lack of effective available therapies. Cancer cell survival is dependent upon up-regulation of the pro-survival response, mediated by anti-apoptotic proteins such as Mcl-1.
Results: Here we show that over-expression of Mcl-1 in pancreatic patient tumor samples is linked to advancement of the disease. We have previously shown that triptolide, a diterpene triepoxide, is effective both in vitro and in vivo, in killing pancreatic cancer cells. Decrease of Mcl-1 levels, either by siRNA or by treatment with triptolide results in cell death. Using pancreatic cancer cell lines, we have shown that miR-204, a putative regulator of Mcl-1, is repressed in cancer cell lines compared to normal cells. Over-expression of miR-204, either by a miR-204 mimic, or by triptolide treatment results in a decrease in Mcl-1 levels, and a subsequent decrease in cell viability. Using luciferase reporter assays, we confirmed the ability of miR-204 to down-regulate Mcl-1 by directly binding to the Mcl-1 3' UTR. Using human xenograft samples treated with Minnelide, a water soluble variant of triptolide, we have shown that miR-204 is up-regulated and Mcl-1 is down-regulated in treated vs. control tumors.
Conclusion: Triptolide mediated miR-204 increase causes pancreatic cancer cell death via loss of Mcl-1.
Details
- Title: Subtitle
- miR-204 mediated loss of Myeloid cell leukemia-1 results in pancreatic cancer cell death
- Creators
- Zhiyu Chen - University of MinnesotaVeena Sangwan - University of MinnesotaSulagna Banerjee - University of MinnesotaTiffany Mackenzie - University of MinnesotaVikas Dudeja - University of MinnesotaXiaowu Li - Army Medical UniversityHuaizhi Wang - Army Medical UniversitySelwyn M Vickers - University of MinnesotaAshok K Saluja - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- Molecular cancer, Vol.12(1), pp.105-105
- DOI
- 10.1186/1476-4598-12-105
- PMID
- 24025188
- PMCID
- PMC3848798
- NLM abbreviation
- Mol Cancer
- ISSN
- 1476-4598
- eISSN
- 1476-4598
- Publisher
- BioMed Central
- Number of pages
- 1
- Language
- English
- Date published
- 09/11/2013
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9985244570902771
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