title: MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets.
abstract: 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.
authors.affiliation: Cancer Genetics, Hormones and Cancer Group, Kolling Institute of Medical Research, Department of Endocrine and Oncology Surgery, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.
authors.forename: Goswin Y
authors.initials: GY
authors.lastname: Meyer-Rochow
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Jackson
authors.forename: John V
authors.initials: JV
authors.lastname: Conaglen
authors.forename: Denis E
authors.initials: DE
authors.lastname: Whittle
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Kunnimalaiyaan
authors.forename: Herbert
authors.initials: H
authors.lastname: Chen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Westin
authors.forename: Johanna
authors.initials: J
authors.lastname: Sandgren
authors.forename: Peter
authors.initials: P
authors.lastname: Stålberg
authors.forename: Elham
authors.initials: E
authors.lastname: Khanafshar
authors.forename: Daniel
authors.initials: D
authors.lastname: Shibru
authors.forename: Quan-Yang
authors.initials: QY
authors.lastname: Duh
authors.forename: Orlo H
authors.initials: OH
authors.lastname: Clark
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.forename: Rory
authors.initials: R
authors.lastname: Clifton-Bligh
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Diana E
authors.initials: DE
authors.lastname: Benn
authors.forename: Stan B
authors.initials: SB
authors.lastname: Sidhu
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle; D015331:Cohort Studies; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010673:Pheochromocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger