MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets. Endocr Relat Cancer 2010 Sep;17(3):835-46
Date
07/14/2010Pubmed ID
20621999DOI
10.1677/ERC-10-0142Scopus ID
2-s2.0-77956387978 (requires institutional sign-in at Scopus site) 73 CitationsAbstract
MicroRNAs (miRNAs) are small RNAs ( approximately 22 bp) that post-transcriptionally regulate protein expression and are found to be differentially expressed in a number of human cancers. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. We performed miRNA microarray expression profiling on a cohort of 12 benign and 12 malignant pheochromocytomas and identified a number of differentially expressed miRNAs. These results were validated in a separate cohort of ten benign and ten malignant samples using real-time quantitative RT-PCR; benign samples had a minimum follow-up of at least 2 years. It was found that IGF2 as well as its intronic miR-483-5p was over-expressed, while miR-15a and miR-16 were under-expressed in malignant tumours compared with benign tumours. These miRNAs were found to be diagnostic and prognostic markers for malignant pheochromocytoma. The functional role of miR-15a and miR-16 was investigated in vitro in the rat PC12 pheochromocytoma cell line, and these miRNAs were found to regulate cell proliferation via their effect on cyclin D1 and apoptosis. These data indicate that miRNAs play a pivotal role in the biology of malignant pheochromocytoma, and represent an important class of diagnostic and prognostic biomarkers and therapeutic targets warranting further investigation.
Author List
Meyer-Rochow GY, Jackson NE, Conaglen JV, Whittle DE, Kunnimalaiyaan M, Chen H, Westin G, Sandgren J, Stålberg P, Khanafshar E, Shibru D, Duh QY, Clark OH, Kebebew E, Gill AJ, Clifton-Bligh R, Robinson BG, Benn DE, Sidhu SBMESH terms used to index this publication - Major topics in bold
Adrenal Gland NeoplasmsAdrenal Glands
Animals
Apoptosis
Biomarkers, Tumor
Blotting, Western
Cell Cycle
Cohort Studies
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
MicroRNAs
Oligonucleotide Array Sequence Analysis
Pheochromocytoma
Prognosis
RNA, Messenger
Rats
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Tumor Cells, Cultured