Search Results

1 - 10 of 12 items :

  • Molecular Biology x
  • Basic Medical Science x
  • Life Sciences x
Clear All

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e Cancer Genome Atlas (TCGA), approximately 40% of PPGLs are due to germ line mutations in one of 16 susceptibility genes, and a further 30% are due to somatic alterations in at least seven main genes (VHL, EPAS1, CSDE1, MAX, HRAS, NF1, RET, and possibly KIF1B). Th e diagnosis of malignant PPGL was straight forward in most cases as it was defined as presence of PPGL in non-chromaffin tissues. Accordingly, there is an extreme need for new diagnostic marker(s) to identify tumors with malignant prospective. Th e aim of this study was to review all suggested genetic and epigenetic alterations that are remarkably different between benign and malignant PPGLs. It seems that more than two genetic mutation clusters in PPGLs and other genetic and methylation biomarkers could be targeted for malignancy discrimination in different studies.

Abstract

Objective. The aim of the present study was to investigate the effect of adipokine NAMPT (nicotinamide phosphoribosyltransferase) silencing on the expression of genes encoding IRS1 (insulin receptor substrate 1) and some other proliferation related proteins in U87 glioma cells for evaluation of the possible significance of this adipokine in intergenic interactions.

Methods. The silencing of NAMPT mRNA was introduced by NAMPT specific siRNA. The expression level of NAMPT, IGFBP3, IRS1, HK2, PER2, CLU, BNIP3, TPD52, GADD45A, and MKI67 genes was studied in U87 glioma cells by quantitative polymerase chain reaction. Anti-visfatin antibody was used for detection of NAMPT protein by Western-blot analysis.

Results. It was shown that the silencing of NAMPT mRNA led to a strong down-regulation of NAMPT protein and significant modification of the expression of IRS1, IGFBP3, CLU, HK2, BNIP3, and MKI67 genes in glioma cells and a strong up-regulation of IGFBP3 and IRS1 and down-regulation of CLU, BNIP3, HK2, and MKI67 gene expressions. At the same time, no significant changes were detected in the expression of GADD45A, PER2, and TPD52 genes in glioma cells treated by siRNA specific to NAMPT. Furthermore, the silencing of NAMPT mRNA suppressed the glioma cell proliferation.

Conclusions. Results of this investigation demonstrated that silencing of NAMPT mRNA with corresponding down-regulation of NAMPT protein and suppression of the glioma cell proliferation affected the expression of IRS1 gene as well as many other genes encoding the proliferation related proteins. It is possible that dysregulation of most of the studied genes in glioma cells after silencing of NAMPT is reflected by a complex of intergenic interactions and that NAMPT is an important factor for genome stability and regulatory mechanisms contributing to the control of glioma cell metabolism and proliferation.

, 1043–1048, 2018. Martinelli D, Catteruccia M, Piemonte F, Pastore A, Tozzi G, Dionisi-Vici C, Pontrelli G, Corsetti T, Livadiotti S, Kheifets V, Hinman A, Shrader WD, Thoolen M, Klein MB, Bertini E, Miller G. EPI-743 reverses the progression of the pediatric mitochondrial disease-genetically defined Leigh Syndrome. Mol Genet Metab 107, 383–388, 2012. McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GR, Thormann A, Flicek P, Cunningham F. The Ensembl Variant Effect Predictor. Genome Biol 17, 122, 2016. Paila U, Chapman BA, Kirchner R, Quinlan AR. GEMINI: integrative

beta cell proliferation. J Biol Chem 283, 8723–8735, 2008. Long J, Edwards T, Signorello LB, Cai Q, Zheng W, Shu XO, Blot WJ. Evaluation of genome-wide association study-identified type 2 diabetes loci in African Americans. Am J Epidemiol 176, 995–1001, 2012. Lyssenko V, Lupi R, Marchetti P, Del Guerra S, Orho-Melander M, Almgren P, Sjogren M, Ling C, Eriksson KF, Lethagen AL, Mancarella R, Berglund G, Tuomi T, Nilsson P, Del Prato S, Groop L. Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J Clin Invest 117, 2155–2163, 2007

References Aure MR, Leivonen SK, Fleischer T, Zhu Q, Overgaard J, Alsner J, Tramm T, Louhimo R, Alnæs GI, Perala M, Busato F, Touleimat N, Tost J, Børresen-Dale AL, Hautaniemi S, Troyanskaya OG, Lingjærde OC, Sahlberg KK, Kristensen VN. Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors. Genome Biol 14, R126, 2013. Bhattacharya S, Aggarwal R, Singh VP, Ramachandran S, Datta M. Downregulation of miRNAs during delayed wound healing in diabetes: Role of Dicer. Mol Med 2015. Chavali V, Tyagi SC, Mishra

SE, Coin LJ, Deng G, Gieger C, Heard-Costa NL, Hottenga JJ, Kuhnel B, Kumar V, Lagou V, Liang L, et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet 43, 1131–1138, 2011. Chi YI, Frantz JD, Oh BC, Hansen L, Dhe-Paganon S, Shoelson SE. Diabetes mutations delineate an atypical POU domain in HNF-1α. Mol Cell 10, 1129–1137, 2002. Chi YI, Frantz JD, Oh BC, Hansen L, Dhe-Paganon S,Shoelson SE. Diabetes mutations delineate an atypical POU domain in HNF-1alpha. Mol Cell 10, 1129–1137, 2002. Chi YI

interleukin-6 receptor alpha. J Clin Invest 100, 2752–2756, 1997. Moraes CF, Lins TC, Carmargos EF, Naves JO, Pereira RW, Nobrega OT. Lessons from genome-wide association studies findings in Alzheimer’s disease. Psychogeriatrics 12, 62–73, 2012. Muller UC, Deller T, Korte M. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat Rev Neurosci 18, 281–298, 2017. Murakami N, Yamaki T, Iwamoto Y, Sakakibara T, Kobori N, Fushiki S, Ueda S. Experimental brain injury induces expression of amyloid precursor protein, which may be related to neuronal

. Molecular Cell 32, 276-284, 2008. http://dx.doi.org/10.1016/j.molcel.2008.09.014 Holley CL, Topkara VK. An introduction to small non-coding RNAs: miRNA and snoRNA. Cardiovasc Drugs Th er 25, 151-159, 2011. http://dx.doi:10.1007/s10557-011-6290-z Hock J, Meister G. The Argonaute protein family. Genome Biol 9, 210, 2008. http://dx.doi.org/10.1186/gb-2008-9-2-210 Hrustincova A, Votavova H, Dostalova Merkerova M. Circulating MicroRNAs: Methodological Aspects in Detection of Th ese Biomarkers.Folia Biologica (Praha) 61, 203−218, 2015. Hu HY, Yan Z, Xu Y, Hu H, Menzel C, Zhou

OPEN ACCESS

and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol 11, 101–111, 2015. Fishbein L, Leshchiner I, Walter V, Danilova L, Robertson AG, Johnson AR, Lichtenberg TM, Murray BA, Ghayee HK, Else T, Ling S, Jefferys SR, de Cubas AA, Wenz B, Korpershoek E, Amelio AL, Makowski L, Rathmell WK, Gimenez-Roqueplo AP, Giordano TJ, Asa SL, Tischler AS; Cancer Genome Atlas Research Network, Pacak K, Nathanson KL, Wilkerson MD. Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell 31, 181–193, 2017. Flynn A, Benn D

. Kinetic and thermodynamic characterization of dihydrotestosterone-induced conformational perturbations in androgen receptor ligand-binding domain. Mol Endocrinol 23, 1231-1241, 2009. Jones S. An overview of the basic helix-loop-helix proteins. Genome Biol 5, 226, 2004. Jung SY, Malovannaya A, Wei J, O’Malley BW, Qin J. Proteomic analysis of steady-state nuclear hormone receptor coactivator complexes. Mol Endocrinol 19, 2451-2465, 2005. Kastner P, Mark M, Chambon P. Nonsteroid nuclear receptors: what are genetic studies telling us about their role in real life? Cell 83