Browse

In vivo imaging of functional targeting of miR-221 in papillary thyroid carcinoma

Cited 51 time in Web of Science Cited 55 time in Scopus
Authors
Kim, Hyun Joo; Kim, Young Ha; Lee, Dong Soo; Chung, June-Key; Kim, Soonhag
Issue Date
2008-09-17
Publisher
The Society of Nuclear Medicine Inc
Citation
J Nucl Med. 2008;49(10):1686-1693
Keywords
AnimalsBase SequenceCarcinoma, Papillary/*diagnosis/*radionuclide imagingCell Line, TumorCodon*Gene Expression Regulation, NeoplasticHomeodomain Proteins/metabolismHumansLuciferases/metabolismMiceMicroRNAs/*biosynthesis/metabolismMolecular Sequence DataOligonucleotide Array Sequence AnalysisThyroid Neoplasms/*diagnosis/*radionuclide imaging
Abstract
MicroRNAs (miRNAs) are small, noncoding RNA molecules that control expression of target genes. The abnormally expressed miRNAs function as oncogenes or tumor suppressors in human cancer. To evaluate the abundant gene regulation of miR-221 in papillary thyroid carcinoma (PTC), we performed microarray analysis and developed a Gaussia luciferase (Gluc) reporter system regulated by miR-221. METHODS: Total RNAs were isolated from pre-miR-221-treated normal human thyroid cells (HT-ori3) and anti-miR-221-treated papillary thyroid cells (NPA). Microarray analysis was performed with 44,000 probes. The messenger RNA levels of target genes regulated by miR-221 were evaluated using reverse-transcription polymerase chain reaction. Three types of cytomegalovirus (CMV)/Gluc_3' untranslated region (UTR) of homeobox B5 (HOXB5), which included a seed sequence of mature miR-221 in the 3' UTR of HOXB5 after the Gluc stop codon, were transfected into NPA cells, and pre-miR-221 was cotransfected with CMV/Gluc_3' UTR of HOXB5. The Gluc activities in cells were measured by luciferase assay. Mice implanted with PTC-expressing Gluc regulated by miR-221 were monitored with bioluminescence imaging for 6 d. RESULTS: Microarray analysis showed thousands of genes were directly and indirectly regulated by miR-221 and shifted the gene expression pattern of normal thyroid cells toward PTC. Of several genes downregulated more than 2-fold by miR-221, messenger RNA levels of HOXB5 were significantly downregulated by miR-221. Also, in vitro or in vivo Gluc activities using CMV/Gluc_3' UTR of HOXB5 systems were downregulated dose dependently by endogenous or exogenous miR-221. CONCLUSION: MiR-221 overexpressed in PTC drives carcinoma gene expression patterns by directly and indirectly regulating numerous genes, including HOXB5. The bioluminescence imaging system using CMV/Gluc_3' UTR of HOXB5 is a useful tool for noninvasive in vivo long-term monitoring of functional targeting of miR-221.
ISSN
0161-5505 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18794255

http://jnm.snmjournals.org/cgi/reprint/49/10/1686.pdf

https://hdl.handle.net/10371/67771
DOI
https://doi.org/10.2967/jnumed.108.052894
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Nuclear Medicine (핵의학전공)Journal Papers (저널논문_핵의학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse