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Alpha-2, 3-sialyltransferases regulate the multidrug resistance of chronic myeloid leukemia through miR-4701-5p targeting ST3GAL1.
- Source :
-
Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 2016 Jul; Vol. 96 (7), pp. 731-40. Date of Electronic Publication: 2016 Apr 18. - Publication Year :
- 2016
-
Abstract
- The aberrant sialylation profile on the surface of leukemia cells has been recognized for its potential diagnostic value towards assessing leukemia multidrug resistance (MDR). MicroRNAs as endogenous regulators of gene expression have been implicated in treating MDR. In this study, we describe the differential expressional profiles of α-2, 3-sialyltransferases (ST) and miR-4701-5p in three pairs of chronic myeloid leukemia (CML) cell lines and 48 clinical samples of bone marrow mononuclear cells from CML patients. The altered expression level of ST3GAL1 was found corresponding to the drug-resistant phenotype (with and without adriamycin resistance) of CML cell lines both in vitro and in vivo. Further the results showed that miR-4701-5p directly targeted ST3GAL1 to reduce CML cells resistance to multiple chemotherapeutics in vitro and to convert tumor cells from adriamycin resistant to susceptible in vivo of mice. These results indicate that differential expression of α-2,3 ST is involved in MDR of CML, and that miR-4701-5p regulates the susceptibility of CML cells to multiple drugs, at least in part, through targeting ST3GAL1.
- Subjects :
- Adolescent
Adult
Aged
Animals
Cell Line, Tumor
Doxorubicin pharmacology
Drug Resistance, Multiple genetics
Drug Resistance, Multiple physiology
Drug Resistance, Neoplasm genetics
Drug Resistance, Neoplasm physiology
Female
Gene Expression Regulation, Neoplastic
Humans
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics
Male
Mice
Mice, Nude
Middle Aged
Sialyltransferases antagonists & inhibitors
Xenograft Model Antitumor Assays
Young Adult
beta-Galactoside alpha-2,3-Sialyltransferase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism
MicroRNAs genetics
MicroRNAs metabolism
Sialyltransferases genetics
Sialyltransferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-0307
- Volume :
- 96
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Publication Type :
- Academic Journal
- Accession number :
- 27088512
- Full Text :
- https://doi.org/10.1038/labinvest.2016.50