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In situ hybridization-based detection of microRNAs in human diseases

14 / Xiongbin Lu2 / Gabriel Lopez-Berestein123 / Anil K. Sood124 / George Calin13

1Center for RNA Interference and Non-coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas

2Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas

3Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas

4Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

This content is open access.
(CC BY-NC-ND 4.0)

Citation Information: microRNA Diagnostics and Therapeutics. Volume 1, Pages 12–23, ISSN (Online) 2084-6843, DOI: 10.2478/micrnat-2013-0002, July 2013

Publication History:
Received:
2013-03-05
Accepted:
2013-05-31
Published Online:
2013-07-29

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that regulate various aspects of gene expression in physiology and development. Links between miRNAs and the initiation and progression of human diseases are becoming increasingly apparent. The development of methods to detect the subcellular and tissue localization of miRNAs is essential for understanding their biological role in homeostasis. In this review, we discuss how in situ hybridization can complement tissuelevel miRNA expression profiling and its role as an investigational tool to better understand the etiology of human diseases. Furthermore, in situ hybridization of miRNAs represents a potent diagnostic assay that could be further refined and utilized for clinical applications.

Keywords: microRNA; in situ hybridization; human diseases; profiling

  • [1] Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, Pasquinelli AE. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell. 2005; 122: 553-63. [CrossRef]

  • [2] Wang Y, Liang Y, Lu Q . MicroRNA epigenetic alterations: predicting biomarkers and therapeutic targets in human diseases. Clin. Genet. 2008; 74: 307-15. [CrossRef]

  • [3] Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat. Struct. Mol. Biol. 2006; 13: 1097-101. [CrossRef]

  • [4] Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004; 432: 235-40. [CrossRef]

  • [5] Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 2002; 297: 2056-60. [CrossRef]

  • [6] Mattick JS, Makunin IV. Non-coding RNA. Hum. Mol. Genet. 2006; 15 Spec No 1: R17-29.

  • [7] Costa FF. Non-coding RNAs: lost in translation? Gene. 2007; 386: 1-10. [CrossRef]

  • [8] Ikeda S, Kong SW, Lu J, Bisping E, Zhang H, Allen PD, Golub TR, Pieske B, Pu WT. Altered microRNA expression in human heart disease. Physiol Genomics. 2007; 31: 367-73. [CrossRef]

  • [9] Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA. 2003; 9: 1274-81. [PubMed] [CrossRef]

  • [10] Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell. 2007; 27: 435-48. [CrossRef]

  • [11] Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME. A brain-specific microRNA regulates dendritic spine development. Nature. 2006; 439: 283-89. [CrossRef]

  • [12] Koshkin AA, Wengel J. Synthesis of Novel 2’,3’-Linked Bicyclic Thymine Ribonucleosides. J. Org. Chem. 1998; 63: 2778-81. [CrossRef]

  • [13] Koshkin AA, Fensholdt J, Pfundheller HM, Lomholt C. A simplified and efficient route to 2’-O, 4’-C-methylene-linked bicyclic ribonucleosides (locked nucleic acid). J. Org. Chem. 2001; 66: 8504-12. [CrossRef]

  • [14] Vester B, Wengel J. LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry. 2004; 43: 13233-41. [CrossRef]

  • [15] Petersen M, Wengel J. LNA: a versatile tool for therapeutics and genomics. Trends Biotechnol. 2003; 21: 74-81. [CrossRef]

  • [16] Braasch DA, Corey DR. Locked nucleic acid (LNA): finetuning the recognition of DNA and RNA. Chem. Biol. 2001; 8: 1-7. [CrossRef]

  • [17] Kurreck J, Wyszko E, Gillen C, Erdmann VA. Design of antisense oligonucleotides stabilized by locked nucleic acids. Nucleic Acids Res. 2002; 30: 1911-8. [CrossRef]

  • [18] Bondensgaard K, Petersen M, Singh SK, Rajwanshi VK, Kumar R, Wengel J, Jacobsen JP. Structural studies of LNA:RNA duplexes by NMR: conformations and implications for RNase H activity. Chemistry. 2000; 6: 2687- 95. [CrossRef]

  • [19] Petersen M, Bondensgaard K, Wengel J, Jacobsen JP. Locked nucleic acid (LNA) recognition of RNA: NMR solution structures of LNA:RNA hybrids. J. Am. Chem. Soc. 2002; 124; 5974-82. [CrossRef]

  • [20] Grunweller A, Hartmann RK. Locked nucleic acid oligonucleotides: the next generation of antisense agents? BioDrugs. 2007; 21: 235-43. [CrossRef]

  • [21] Nuovo GJ. In situ detection of precursor and mature microRNAs in paraffin embedded, formalin fixed tissues and cell preparations. Methods. 2008; 44: 39-46. [CrossRef]

  • [22] Jorgensen S, Baker A, Moller S, Nielsen BS. Robust one-day in situ hybridization protocol for detection of microRNAs in paraffin samples using LNA probes. Methods. 2010; 52: 375-81. [CrossRef]

  • [23] Sempere LF, Preis M, Yezefski T, Ouyang H, Suriawinata AA, Silahtaroglu A, Conejo-Garcia JR, Kauppinen S, Wells W, Korc M. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered MicroRNA expression in solid tumors. Clin. Cancer Res. 2010; 16: 4246-55. [CrossRef]

  • [24] Obernosterer G, Martinez J, Alenius M. Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections. Nat. Protoc. 2007; 2: 1508-14. [CrossRef]

  • [25] Silahtaroglu AN, Nolting D, Dyrskjot L, Berezikov E, Moller M, Tommerup N, Kauppinen S. Detection of microRNAs in frozen tissue sections by fluorescence in situ hybridization using locked nucleic acid probes and tyramide signal amplification. Nat. Protoc.2007; 2: 2520-28. [CrossRef]

  • [26] Thompson RC, Deo M, Turner DL. Analysis of microRNA expression by in situ hybridization with RNA oligonucleotide probes. Methods. 2007; 43: 153-61. [CrossRef]

  • [27] Pena JT, Sohn-Lee C, Rouhanifard SH, Ludwig J, Hafner M, Mihailovic A, Lim C, Holoch D, Berninger P, Zavolan M, Tuschl T. miRNA in situ hybridization in formaldehyde and EDC-fixed tissues. Nat. Methods. 2009; 6: 139-41. [CrossRef]

  • [28] Kloosterman WP, Wienholds E, de BE, Kauppinen S, Plasterk RH. In situ detection of miRNAs in animal embryos using LNA-modified oligonucleotide probes. Nat. Methods. 2006; 3: 27-9. [CrossRef]

  • [29] Pearson BJ, Eisenhoffer GT, Gurley KA, Rink JC, Miller DE, Sanchez AA. Formaldehyde-based whole-mount in situ hybridization method for planarians. Dev. Dyn. 2009; 238: 443-50. [CrossRef]

  • [30] Lu J, Tsourkas A. Imaging individual microRNAs in single mammalian cells in situ. Nucleic Acids Res. 2009; 37: e100. [CrossRef]

  • [31] Nuovo G, Lee EJ, Lawler S, Godlewski J, Schmittgen T. In situ detection of mature microRNAs by labeled extension on ultramer templates. Biotechniques. 2009; 46: 115-26. [CrossRef]

  • [32] Christodoulou F, Raible F, Tomer R, Simakov O, Trachana K, Klaus S, Snyman H, Hannon GJ, Bork P, Arendt D. Ancient animal microRNAs and the evolution of tissue identity. Nature. 2010; 463: 1084-8. [CrossRef]

  • [33] Schad A, Fahimi HD, Volkl A, Baumgart E. Expression of catalase mRNA and protein in adult rat brain: detection by nonradioactive in situ hybridization with signal amplification by catalyzed reporter deposition (ISH-CARD) and immunohistochemistry (IHC)/immunofluorescence (IF). J. Histochem. Cytochem. 2003; 51: 751-60. [CrossRef]

  • [34] Preis M, Gardner TB, Gordon SR, Pipas JM, Mackenzie TA, Klein EE, Longnecker DS, Gutmann EJ, Sempere LF, Korc M. MicroRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clin. Cancer Res. 2011; 17: 5812-21. [CrossRef]

  • [35] Nuovo GJ, Elton TS, Nana-Sinkam P, Volinia S, Croce CM, Schmittgen TD. A methodology for the combined in situ analyses of the precursor and mature forms of microRNAs and correlation with their putative targets. Nat. Protoc. 2009; 4: 107-15. [CrossRef]

  • [36] Nicoloso MS, Calin GA. MicroRNA involvement in brain tumors: from bench to bedside. Brain Pathol. 2008; 18: 122- 9. [CrossRef]

  • [37] Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, Liu CG, Calin GA, Croce CM, Harris CC. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008; 299: 425-36.

  • [38] Streit S, Michalski CW, Erkan M, Kleeff J, Friess H. Northern blot analysis for detection and quantification of RNA in pancreatic cancer cells and tissues. Nat. Protoc. 2009; 4: 37-43.

  • [39] Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 2004; 5: R13. [CrossRef]

  • [40] Liu CG, Spizzo R, Calin GA, Croce CM. Expression profiling of microRNA using oligo DNA arrays. Methods; 44: 22-30.

  • [41] Schmittgen TD, Jiang J, Liu Q, Yang L. A high-throughput method to monitor the expression of microRNA precursors. Nucleic Acids Res. 2004; 32: e43. [CrossRef]

  • [42] Nolan T, Hands RE, Bustin SA. Quantification of mRNA using real-time RT-PCR. Nat. Protoc. 2006; 1: 1559-82. [CrossRef]

  • [43] Chen J, Lozach J, Garcia EW, Barnes B, Luo S, Mikoulitch I, Zhou L, Schroth G, Fan JB. Highly sensitive and specific microRNA expression profiling using BeadArray technology. Nucleic Acids Res. 2008; 36: e87. [CrossRef]

  • [44] Shendure J, Ji H. Next-generation DNA sequencing. Nat. Biotechnol. 2008; 26: 1135-45. [CrossRef]

  • [45] Mardis ER. The impact of next-generation sequencing technology on genetics. Trends Genet. 2008; 24: 133-41. [CrossRef]

  • [46] Rung J, Brazma A. Reuse of public genome-wide gene expression data. Nat. Rev. Genet. 2013; 14: 89-99.

  • [47] ‘t Hoen PA, Ariyurek Y, Thygesen HH, Vreugdenhil E, Vossen RH, de Menezes RX, Boer JM, van Ommen GJ, den Dunnen JT. Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms. Nucleic Acids Res. 2008; 36, e141. [CrossRef]

  • [48] Creighton CJ, Reid JG, Gunaratne PH. Expression profiling of microRNAs by deep sequencing. Brief. Bioinform. 2009; 10: 490-7. [CrossRef]

  • [49] Branton D, Deamer DW, Marziali A, Bayley H, Benner SA, Butler T, Di VM, Garaj S, Hibbs A, Huang X, Jovanovich SB, Krstic PS, Lindsay S, Ling XS, Mastrangelo CH, Meller A, Oliver JS, Pershin YV, Ramsey JM, Riehn R, Soni GV, Tabard- Cossa V, Wanunu M, Wiggin M, Schloss JA. The potential and challenges of nanopore sequencing. Nat. Biotechnol. 2008; 26: 1146-53. [CrossRef]

  • [50] Wolber PK, Collins PJ, Lucas AB, De WA, Shannon KW. The Agilent in situ-synthesized microarray platform. Methods Enzymol. 2006; 410: 28-57. [CrossRef]

  • [51] Hughes TR, Hiley SL, Saltzman AL, Babak T, Blencowe BJ. Microarray analysis of RNA processing and modification. Methods Enzymol. 2006; 410: 300-16. [CrossRef]

  • [52] Kong W, Zhao JJ, He L, Cheng JQ . Strategies for profiling microRNA expression. J. Cell Physiol. 2009; 218: 22-5. [CrossRef]

  • [53] Murphy J, Bustin SA. Reliability of real-time reversetranscription PCR in clinical diagnostics: gold standard or substandard? Expert. Rev. Mol. Diagn. 2009; 9: 187-97. [CrossRef]

  • [54] Lee YS, Dutta A. MicroRNAs in cancer. Annu. Rev. Pathol. 2009; 4: 199-227. [CrossRef]

  • [55] Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 2999-3004. [CrossRef]

  • [56] Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat. Rev. Cancer. 2006; 6: 857-66. [CrossRef]

  • [57] Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65: 7065-70. [CrossRef]

  • [58] Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 2257-61. [CrossRef]

  • [59] Yamamichi N, Shimomura R, Inada K, Sakurai K, Haraguchi T, Ozaki Y, Fujita S, Mizutani T, Furukawa C, Fujishiro M, Ichinose M, Shiogama K, Tsutsumi Y, Omata M, Iba H. Locked nucleic acid in situ hybridization analysis of miR- 21 expression during colorectal cancer development. Clin. Cancer Res. 2009; 15: 4009-16. [CrossRef]

  • [60] Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J. Gastrointest. Surg. 2008; 12: 2171-76. [CrossRef]

  • [61] Hermansen SK, Dahlrot RH, Nielsen BS, Hansen S, Kristensen BW. MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas. J. Neurooncol. 2013; 111: 71-81. [CrossRef]

  • [62] Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006; 9: 189-98. [CrossRef]

  • [63] Donnem T, Eklo K, Berg T, Sorbye SW, Lonvik K, Al-Saad S, Al-Shibli K, Andersen S, Stenvold H, Bremnes RM, Busund LT. Prognostic impact of MiR-155 in non-small cell lung cancer evaluated by in situ hybridization. J. Transl. Med. 2011; 9: 6.

  • [64] Ryu JK, Hong SM, Karikari CA, Hruban RH, Goggins MG, Maitra A. Aberrant MicroRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma. Pancreatolog. 2010; 10: 66-73. [CrossRef]

  • [65] Quesne JL, Jones J, Warren J, Dawson SJ, Ali HR, Bardwell H, Blows F, Pharoah P, Caldas C. Biological and prognostic associations of miR-205 and let-7b in breast cancer revealed by in situ hybridization analysis of micro-RNA expression in arrays of archival tumour tissue. J. Pathol. 2012; 227: 306- 14. [CrossRef]

  • [66] Hanna JA, Hahn L, Agarwal S, Rimm DL. In situ measurement of miR-205 in malignant melanoma tissue supports its role as a tumor suppressor microRNA. Lab Invest. 2012; 92: 1390- 97. [CrossRef]

  • [67] Hansen TF, Sorensen FB, Lindebjerg J, Jakobsen A. The predictive value of microRNA-126 in relation to first line treatment with capecitabine and oxaliplatin in patients with metastatic colorectal cancer. BMC. Cancer. 2012; 12: 83. [CrossRef]

  • [68] Catalucci D, Gallo P, Condorelli G. MicroRNAs in cardiovascular biology and heart disease. Circ. Cardiovasc. Genet. 2009; 2: 402-8. [CrossRef]

  • [69] Chen JF, Murchison EP, Tang R, Callis TE, Tatsuguchi M, Deng Z, Rojas M, Hammond SM, Schneider MD, Selzman CH, Meissner G, Patterson C, Hannon GJ, Wang DZ. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 2111-6. [CrossRef]

  • [70] Malizia AP, Wang DZ. MicroRNAs in cardiomyocyte development. Wiley. Interdiscip. Rev. Syst. Biol. Med. 2011; 3: 183-90. [CrossRef]

  • [71] Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T. Increased microRNA-1 and microRNA- 133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ. Cardiovasc. Genet. 2011; 4: 446-54.

  • [72] Torella D, Iaconetti C, Catalucci D, Ellison GM, Leone A, Waring CD, Bochicchio A, Vicinanza C, Aquila I, Curcio A, Condorelli G, Indolfi C. MicroRNA-133 controls vascular smooth muscle cell phenotypic switch in vitro and vascular remodeling in vivo. Circ. Res. 2011; 109: 880-93. [CrossRef]

  • [73] Wang YS, Wang HY, Liao YC, Tsai PC, Chen KC, Cheng HY, Lin RT, Juo SH. MicroRNA-195 regulates vascular smooth muscle cell phenotype and prevents neointimal formation. Cardiovasc. Res. 2012; 95: 517-26. [CrossRef]

  • [74] Gambardella S, Rinaldi F, Lepore SM, Viola A, Loro E, Angelini C, Vergani L, Novelli G, Botta A. Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients. J. Transl. Med. 2010; 8: 48.

  • [75] Larsson E, Fredlund FP, Heldin J, Barkefors I, Bondjers C, Genove G, Arrondel C, Gerwins P, Kurschat C, Schermer B, Benzing T, Harvey SJ, Kreuger J, Lindahl P. Discovery of microvascular miRNAs using public gene expression data: miR-145 is expressed in pericytes and is a regulator of Fli1. Genome Med. 2009; 1: 108.

  • [76] Schneider M, Andersen DC, Silahtaroglu A, Lyngbaek S, Kauppinen S, Hansen JL, Sheikh SP. Cell-specific detection of microRNA expression during cardiomyogenesis by combined in situ hybridization and immunohistochemistry. J. Mol. Histol. 2011; 42: 289-99. [CrossRef]

  • [77] Junn E, Mouradian MM. MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol. Ther. 2012; 133: 142-50. [CrossRef]

  • [78] Nelson PT, Wang WX, Rajeev BW. MicroRNAs (miRNAs) in neurodegenerative diseases. Brain Pathol. 2008; 18: 130- 8. [CrossRef]

  • [79] Wang WX, Rajeev BW, Stromberg AJ, Ren N, Tang G, Huang Q, Rigoutsos I, Nelson PT. The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J. Neurosci. 2008; 28: 1213-23.

  • [80] Kapsimali M, Kloosterman WP, de BE, Rosa F, Plasterk RH, Wilson SW. MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system. Genome Bio. 2007; 8: R173. [CrossRef]

  • [81] Hebert SS, Sergeant N, Buee L. MicroRNAs and the Regulation of Tau Metabolism. Int. J. Alzheimers. Dis. 2012; 2012: 406561.

  • [82] Hebert SS, Papadopoulou AS, Smith P, Galas MC, Planel E, Silahtaroglu AN, Sergeant N, Buee L, De SB. Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration. Hum. Mol. Genet. 2010; 19: 3959-69. [CrossRef]

  • [83] Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y, Cannon B, Kelnar K, Kemppainen J, Brown D, Chen C, Prinjha RK, Richardson JC, Saunders AM, Roses AD, Richards CA. Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J. Alzheimers. Dis. 2008; 14: 27-41.

  • [84] Lukiw WJ. Micro-RNA speciation in fetal, adult and Alzheimer’s disease hippocampus. Neuroreport. 2007; 18: 297-300. [CrossRef]

  • [85] Delay C, Mandemakers W, Hebert SS. MicroRNAs in Alzheimer’s disease. Neurobiol. Dis. 2012; 46: 285-90. [CrossRef]

  • [86] Hebert SS, Horre K, Nicolai L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN, Kauppinen S, Delacourte A, De SB. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proc. Natl. Acad. Sci. U. S. A. 2008; 105: 6415-20.

  • [87] Liu W, Liu C, Zhu J, Shu P, Yin B, Gong Y, Qiang B, Yuan J, Peng X. MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimer’s-associated pathogenesis in SAMP8 mice. Neurobiol. Aging. 2012; 33: 522-34. [CrossRef]

  • [88] Nelson PT, Dimayuga J, Wilfred BR. MicroRNA in Situ Hybridization in the Human Entorhinal and Transentorhinal Cortex. Front Hum. Neurosci. 2012; 4: 7.

  • [89] Minones-Moyano E, Porta S, Escaramis G, Rabionet R, Iraola S, Kagerbauer B, Espinosa-Parrilla Y, Ferrer I, Estivill X, Marti E. MicroRNA profiling of Parkinson’s disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum. Mol. Genet. 2011; 20: 3067-78. [CrossRef]

  • [90] Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL. The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington’s disease. J. Neurosci. 2008; 28: 14341-6. [CrossRef]

  • [91] Tan SL, Ohtsuka T, Gonzalez A, Kageyama R. MicroRNA9 regulates neural stem cell differentiation by controlling Hes1 expression dynamics in the developing brain. Genes Cells. 2012; 17: 952-61.

  • [92] Nelson PT, Wilfred BR. In situ hybridization is a necessary experimental complement to microRNA (miRNA) expression profiling in the human brain. Neurosci. Lett. 2009; 466: 69-72. [CrossRef]

  • [93] Karginov FV, Conaco C, Xuan Z, Schmidt BH, Parker JS, Mandel G, Hannon GJ. A biochemical approach to identifying microRNA targets. Proc. Natl. Acad. Sci. U. S. A. 2007; 104: 19291-6. [CrossRef]

  • [94] Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat. Rev. Genet. 2009; 10: 155-9. [CrossRef]

  • [95] Esteller M. Non-coding RNAs in human disease. Nat. Rev. Genet. 2011; 12: 861-74. [CrossRef]

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