Journal
BIOCHEMICAL PHARMACOLOGY
Volume 87, Issue 4, Pages 562-570Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2013.12.004
Keywords
miR-30d; Autophagy; Apoptosis; Beclin1; Cisplatin; Anaplastic thyroid cancer
Categories
Funding
- National Natural Sciences Foundation of China [81072146, 81101913]
- Natural Science Foundation of Jiangsu provincial Colleges and Universities [12KJD310005]
- Science and Technology Foundation of Suzhou City [SYS201319]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- US Public Health Service [R01CA135038]
- Elsa Pardee Foundation
Ask authors/readers for more resources
miR-30d has been observed to be significantly down-regulated in human anaplastic thyroid carcinoma (ATC), and is believed to be an important event in thyroid cell transformation. In this study, we found that miR-30d has a critical role in modulating sensitivity of ATC cells to cisplatin, a commonly used chemotherapeutic drug for treatment of this neoplasm. Using a mimic of miR-30d, we demonstrated that miR-30d could negatively regulate the expression of beclin 1, a key autophagy gene, leading to suppression of the cisplatin-activated autophagic response that protects ATC cells from apoptosis. A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3' UTR was the region required for the inhibition of beclin 1 expression by this miRNA. We further showed that inhibition of the beclin 1-mediated autophagy by the miR-30d mimic sensitized ATC cells to cisplatin both in vitro (cell culture) and in vivo (animal xenograft model). These results suggest that dysregulation of miR-30d in ATC cells is responsible for the insensitivity to cisplatin by promoting autophagic survival. Thus, miR-30d may be exploited as a potential target for therapeutic intervention in the treatment of ATC. (C) 2013 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available