PMID- 24446485 OWN - NLM STAT- MEDLINE DCOM- 20140430 LR - 20181202 IS - 1479-683X (Electronic) IS - 0804-4643 (Linking) VI - 170 IP - 4 DP - 2014 Apr TI - MicroRNA expression patterns associated with hyperfunctioning and non-hyperfunctioning phenotypes in adrenocortical adenomas. PG - 583-91 LID - 10.1530/EJE-13-0817 [doi] AB - BACKGROUND: The adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression. AIM: To characterize miRNA expression profile in relation to the subtypes of ACAs. SUBJECTS AND METHODS: miRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR. RESULTS: An hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes. CONCLUSION: The results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics. FAU - Velazquez-Fernandez, David AU - Velazquez-Fernandez D AD - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. FAU - Caramuta, Stefano AU - Caramuta S FAU - Ozata, Deniz M AU - Ozata DM FAU - Lu, Ming AU - Lu M FAU - Hoog, Anders AU - Hoog A FAU - Backdahl, Martin AU - Backdahl M FAU - Larsson, Catharina AU - Larsson C FAU - Lui, Weng-Onn AU - Lui WO FAU - Zedenius, Jan AU - Zedenius J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140308 PL - England TA - Eur J Endocrinol JT - European journal of endocrinology JID - 9423848 RN - 0 (MicroRNAs) RN - 4964P6T9RB (Aldosterone) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - Adolescent MH - Adrenal Cortex/*metabolism MH - Adrenal Cortex Neoplasms/*genetics/metabolism MH - Adrenocortical Adenoma/*genetics/metabolism MH - Adult MH - Aged MH - Aged, 80 and over MH - Aldosterone/metabolism MH - Cohort Studies MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic/*genetics MH - Humans MH - Hydrocortisone/metabolism MH - Male MH - MicroRNAs/*genetics MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis MH - Reverse Transcriptase Polymerase Chain Reaction MH - Young Adult EDAT- 2014/01/22 06:00 MHDA- 2014/05/03 06:00 CRDT- 2014/01/22 06:00 PHST- 2014/01/22 06:00 [entrez] PHST- 2014/01/22 06:00 [pubmed] PHST- 2014/05/03 06:00 [medline] AID - EJE-13-0817 [pii] AID - 10.1530/EJE-13-0817 [doi] PST - epublish SO - Eur J Endocrinol. 2014 Mar 8;170(4):583-91. doi: 10.1530/EJE-13-0817. Print 2014 Apr.