000			03158na a2200421 4500
999			_c7940 _d7940
003			PC7940
005			20181026134818.0
008			130622s2013 xxx||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_aBernal González, Carmen _92130 _eEndocrinología y Nutrición
245	0	0	_aIntegrative analysis of miRNA and mRNA expression profiles in pheochromocytoma and paraganglioma identifies genotype-specific markers and potentially regulated pathways. _h[artículo]
260			_bEndocrine-Related Cancer, _c2013
300			_a20(4):477-93.
500			_aFormato Vancouver: De Cubas AA, Leandro-García LJ, Schiavi F, Mancikova V, Comino-Méndez I,Inglada-Pérez L et al. Integrative analysis of miRNA and mRNA expression profiles in pheochromocytoma and paraganglioma identifies genotype-specific markers and potentially regulated pathways. Endocr Relat Cancer. 2013 Jun 24;20(4):477-93.
501			_aPMID: 23660872
504			_aContiene 71 referencias
520			_aPheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasias of neural crest origin that can be part of several inherited syndromes. Although their mRNA profiles are known to depend on genetic background, a number of questions related to tumor biology and clinical behavior remain unanswered. As microRNAs (miRNAs) are key players in the modulation of gene expression, their comprehensive analysis could resolve some of these issues. Through characterization of miRNA profiles in 69 frozen tumors with germline mutations in the genes SDHD, SDHB, VHL, RET, NF1, TMEM127, and MAX, we identified miRNA signatures specific to, as well as common among, the genetic groups of PCCs/PGLs. miRNA expression profiles were validated in an independent series of 30 composed of VHL-, SDHB-, SDHD-, and RET-related formalin-fixed paraffin-embedded PCC/PGL samples using quantitative real-time PCR. Upregulation of miR-210 in VHL- and SDHB-related PCCs/PGLs was verified, while miR-137 and miR-382 were confirmed as generally upregulated in PCCs/PGLs (except in MAX-related tumors). Also, we confirmed overexpression of miR-133b as VHL-specific miRNAs, miR-488 and miR-885-5p as RET-specific miRNAs, and miR-183 and miR-96 as SDHB-specific miRNAs. To determine the potential roles miRNAs play in PCC/PGL pathogenesis, we performed bioinformatic integration and pathway analysis using matched mRNA profiling data that indicated a common enrichment of pathways associated with neuronal and neuroendocrine-like differentiation. We demonstrated that miR-183 and/or miR-96 impede NGF-induced differentiation in PC12 cells. Finally, global proteomic analysis in SDHB and MAX tumors allowed us to determine that miRNA regulation occurs primarily through mRNA degradation in PCCs/PGLs, which partially confirmed our miRNA-mRNA integration results.
710			_9292 _aServicio de Endocrinología y Nutrición
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/7/pc7940.pdf _ySolicitar documento
942			_n0 _2ddc _cART