title: Downregulation of miR-375 in aldosterone-producing adenomas promotes tumour cell growth via MTDH.
abstract: OBJECTIVE
  Previous studies have investigated the genetic and molecular basis of primary aldosteronism (PA), a common cause of human hypertension, but the effects of microRNAs (miRNAs) on the adrenocortical cell proliferation and aldosterone production are largely obscure. Here, we characterized miRNA expression patterns in the subtypes of PA to gain a better understanding of its pathogenesis.
  
  
  METHODS
  miRNA expression was assessed by microarray profiling analysis in aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia (UAH) and normal adrenal cortex tissues. Selected differentially expressed miRNAs were further validated in a validation cohort by qRT-PCR. A gain-of-function approach was used to explore the functional role of the specific miRNA in vitro.
  
  
  RESULTS
  Of 31 miRNAs including miR-375, miR-7 and miR-29b were found to be significantly differentially expressed among these three groups. miR-375 was the most downregulated one in adrenal cortex tissues from PA patients, and its expression level was inversely correlated with the tumour size in APA. Overexpression of miR-375 in a human adrenocortical cell line (H295R) reduced cell proliferation and suppressed the expression of MTDH (metadherin, also known as astrocyte elevated gene-1). Moreover, MTDH was verified as a direct target of miR-375 through luciferase reporter assays. Knock-down of MTDH in H295R cells attenuated Akt-Ser473 phosphorylation and inhibited cell viability.
  
  
  CONCLUSIONS
  Our findings suggest that miR-375 exerts its tumour-suppressive function via targeting MTDH/Akt pathway and implicate a potential therapeutic target in PA.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: He
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tingwei
authors.initials: T
authors.lastname: Su
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Science (SIBS), Chinese Academy of Science (CAS), Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000236:Adenoma; D000302:Adrenal Cortex / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins; D035683:MicroRNAs / Q000235:genetics*; D016601:RNA-Binding Proteins
chemical_list: D015815:Cell Adhesion Molecules; C540933:MIRN375 microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D000450:Aldosterone