Background
Investigating BRAF(V600E) inhibitors (BRAFi) as a strategy to treat patients with aggressive thyroid tumors
harboring the BRAF(V600E) mutant currently is in progress, and drug resistance is expected to pose a challenge.
MicroRNAs (miRNAs) are involved in development of resistance to a variety of drugs
in different malignancies.
Methods
miRNA expression profiles in the human anaplastic thyroid cancer cell line (8505c)
were compared with its PLX4720-resistant counterpart (8505c-R) by the use of Illumina
deep sequencing. We conducted a functional annotation and pathway analysis of the
putative and experimentally validated target genes of the significantly altered miRNAs.
Results
We identified 61 known and 2 novel miRNAs whose expression was altered greatly in
8505c-R. Quantitative reverse-transcription polymerase chain reaction validated altered
expression of 7 selected miRNAs in 8505c-R and BCPAP-R (PLX4720-resistant papillary
thyroid cancer cell line). We found 14 and 25 miRNAs whose expression levels changed
substantially in 8505c and 8505c-R, respectively, after treatment with BRAFi. The
mitogen-activated protein kinase and phosphatidylinositol 3-kinase-AKT pathways were
among the prominent targets of many of the deregulated miRNAs.
Conclusion
We have identified a number of miRNAs that could be used as biomarkers of resistance
to BRAFi in patients with thyroid cancer. In addition, these miRNAs can be explored
as potential therapeutic targets in combination with BRAFi to overcome resistance.
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Article info
Publication history
Published online: October 05, 2015
Accepted:
June 5,
2015
Footnotes
Supported by The National Institutes of Health grant to Dr. Sareh Parangi (NIH-NCI R01 1R01CA149738-01A1). Dr. Eran Brauner's work was sponsored by a grant from the Clair and Emanuel G. Rosenblatt fund and the American Healthcare Professionals and Friends for Medicine in Israel (APF).
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
