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Open Access 01-12-2007 | Research

Effect of BRAF^V600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model

Authors: Susanne Cahill, Paul Smyth, Karen Denning, Richard Flavin, Jinghuan Li, Astrid Potratz, Simone M Guenther, Richard Henfrey, John J O'Leary, Orla Sheils

Published in: Molecular Cancer | Issue 1/2007

Abstract

Background

microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nucleotides in length that have been found to control cell growth, differentiation and apoptosis. They negatively regulate target genes and have recently been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. Recently, a point mutation in the BRAF gene leading to a V600E substitution has been identified as the most common genetic change in papillary thyroid carcinoma (PTC) occurring in 29–69% of cases. This mutation leads to aberrant MAPK activation that is implicated in tumourigenesis.

Aim

The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis.

Results

A unique miRNA expression signature differentiated between PTC cell lines with BRAF mutations and a normal thyroid cell line. 15 miRNAs were found to be upregulated and 23 miRNAs were downregulated. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. miRNA profiling will assist in the elucidation of disease pathogenesis and identification biomarkers and targets.

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Kondo T, Ezzat S, Asa SL: Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006, 6 (4): 292-306. 10.1038/nrc1836CrossRefPubMed

Sheils O: Molecular classification and biomarker discovery in papillary thyroid carcinoma. Expert Rev. Mol. Diagn. 2005, 5 (6): 927-946. 10.1586/14737159.5.6.927CrossRefPubMed

Nikiforova MN, Kimura ET, Gandhi M: BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003, 88: 5399-5404. 10.1210/jc.2003-030838CrossRefPubMed

Xing M: BRAF mutation in thyroid cancer. Endocrin Rel Cancer. 2005, 12: 245-262. 10.1677/erc.1.0978.CrossRef

Finley DJ, Arora N, Zhu B: Molecular profiling distinguishes papillary carcinoma from benign thyroid nodules. J Clin Endocrinol Metab. 2004, 89: 3214-3223. 10.1210/jc.2003-031811CrossRefPubMed

Huang Y, Prasad M, Lemon WJ: Gene expression in papillary thyroid carcinoma reveals highly consistent profiles. Proc Natl Acad Sci USA. 2001, 98 (26): 15044-15049. 10.1073/pnas.251547398PubMedCentralCrossRefPubMed

Jarzab B, Wiench M, Fujarewicz K, Simek K, Jarzab M, Oczko-Wojciechowskam , Wloch J, Czarniecka A, Cmielik E, Lange D, Daulaczek A, Szpak S, Gubala E: Gene Expression Profile of Papillary Thyroid Cancer: Sources of Variability and Diagnostic Implications. Cancer Res. 2005, 65: 1587-1597. 10.1158/0008-5472.CAN-04-3078CrossRefPubMed

Lee RC, Feinbaum RL, Ambros V: The C-elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993, 75: 843-854. 10.1016/0092-8674(93)90529-YCrossRefPubMed

Feinbaum R, Ambros V: The Timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans. Dev Biol. 1999, 210: 87-95. 10.1006/dbio.1999.9272CrossRefPubMed

10.

Zhang B, Pan X, Cobb GP, Anderson TA: microRNAs as oncogenes and tumour suppressors. Dev Biol. 2007, 302 (1): 1-12. 10.1016/j.ydbio.2006.08.028CrossRefPubMed

11.

Zhang B, Pan X, Wang Q, Cobb GP, Anderson TA: Computational identification of microRNAs and their targets. Comput Biol Chem. 2006, 30 (6): 395-407. 10.1016/j.compbiolchem.2006.08.006CrossRefPubMed

12.

Esquela-Kerscher A, Slack FJ: Oncomirs-MicroRNAs with a role in cancer. Nat Rev Cancer. 2006, 6 (4): 259-269. 10.1038/nrc1840CrossRefPubMed

13.

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 USA. 2004, 101 (9): 2999-3004. 10.1073/pnas.0307323101PubMedCentralCrossRefPubMed

14.

Hwang HW, Mendell JT: MicroRNAs in cell proliferation, cell death and tumourigensis. B J Cancer. 2006, 94: 776-780. 10.1038/sj.bjc.6603023.CrossRef

15.

Miska EA: How MicroRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 2005, 15: 563-568. 10.1016/j.gde.2005.08.005CrossRefPubMed

16.

Baskerville S, Bartel DP: Microarray profiling of microRNAs reveals frequent coexpression with neighbouring miRNAs and host genes. RNA. 2005, 3: 241-247. 10.1261/rna.7240905.CrossRef

17.

Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, Dell'Aquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM: MicroRNA profiling reveals distinct signature in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA. 2004, 11755-11760.

18.

Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Maira G, Croce CM, Farace MG: Extensive modulation of a set of micrornas in primary glioblastoma. Biochem Biophys Res Commun. 2005, 334: 1351-8. 10.1016/j.bbrc.2005.07.030CrossRefPubMed

19.

Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz R, Golub TR: MicroRNA expression profiles classify human cancers. Nature. 2005, 435 (7045): 834-838. 10.1038/nature03702CrossRefPubMed

20.

Murakami Y, Yasuda T, Saigo T, Toyoda H, Okanoue T, Shimotohno K: Comprehansive analysis of microRNA expression patterns in heptaceulluar carcinoma and non tumourous tissue. Oncogene. 2006, 25: 2537-2545. 10.1038/sj.onc.1209283CrossRefPubMed

21.

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 USA. 2006, 103 (7): 2257-61. 10.1073/pnas.0510565103PubMedCentralCrossRefPubMed

22.

Roldo C, Missiaglia E, Hagan JP, Falconi M, Capelli P, Bersani S, Calin GA, Volinia S, Liu CG, Scarpa A, Croce CM: MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 2006, 4677-84. 29,

23.

Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru C, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM: An oligonucleotide microchip for genome wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA. 2004, 101: 9740-9744. 10.1073/pnas.0403293101PubMedCentralCrossRefPubMed

24.

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: 7065-7070. 10.1158/0008-5472.CAN-05-1783CrossRefPubMed

25.

Michael MZ, O'Connor Sm, Holst Pellekaan NG, Young GP, James RJ: Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003, 1 (12): 882-91.PubMed

26.

Krek A, Grun D, Poy M, Wolf R, Rosenburg L, Epstein EJ, MacMenamin P, da Piedade I, Grunsalus K, Stoffel M, Rajewsky N: Combinatorial MicroRNA Target Predictions. Nat Genet. 2005, 37: 495-500. 10.1038/ng1536CrossRefPubMed

27.

Lewis BP, Shih I, Jones-Rhoades MW, Bartel DP, Burge CB: Prediction of Mammalian MicroRNA Targets. Cell. 2005, 115: 787-798. 10.1016/S0092-8674(03)01018-3.CrossRef

28.

Griffiths-Jones S, Grocock RJ, Van Dongen S, Bateman A, Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acid Res. 2006, 34: 140-144. 10.1093/nar/gkj112CrossRef

29.

Bandres E, Cubedo E, Agirre X, Malumbres R, Zarate R, Ramirez N, Abajo A, Navarro A, Moreno I, Monzo M, Garcia-Foncillas J: Identification by real time PCR of 13 mature mirnas differentially expressed in colorectal cancer and nontumoural tissues. Mol Cancer. 2006, 5: 29- 10.1186/1476-4598-5-29PubMedCentralCrossRefPubMed

30.

Cimmino A, Calin GA, Fabbri M, Lorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM: mir-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005, 102: 13944-13949. 10.1073/pnas.0506654102PubMedCentralCrossRefPubMed

31.

Cummins JM, Yiping H, Pagliarini R, Diaz L, Sjobiom T, Barad O, Bentawich Z, Szafranaska AE, labourier E, Raymond CK, Roberts BS, Juhl H, Kinzier KW, Vogelstein B, Velculescu VE: The colorectal microRNAome. Proc Natl Acad Sci USA. 2006, 103 (10): 3687-3692. 10.1073/pnas.0511155103PubMedCentralCrossRefPubMed

32.

Johnson ST, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labouier E, Reinert KL, Brown D, Slack FJ: Ras is regulated by the let-7 microRNA family. Cell. 2005, 120: 635-647. 10.1016/j.cell.2005.01.014CrossRefPubMed

33.

Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, Jones PA: Specific activation of microRNA-127 with downregulation of the protooncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 2006, 9 (6): 435-43. 10.1016/j.ccr.2006.04.020CrossRefPubMed

34.

Feili N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F, Liuzzi F, Lulli V, Morsilli O, Santoro S, Valtieri M, Calin GA, Liu CG, Sorrentino A, Croce CM, Peschie C: MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA. 2005, 102: 18081-18066. 10.1073/pnas.0506216102CrossRef

35.

Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota Y, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006, 9;: 189-198. 10.1016/j.ccr.2006.01.025CrossRefPubMed

36.

Huiling H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, De la Chapelle A: The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 102: 19075-19080.

37.

Pallante P, Viscone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappette G, Liu CG, Santoro M, Negrini M, Croce CM, Fusco A: MicroRNA deregulation in human papillary thyroid carcinomas. Endocr Relat Cancer. 2006, 13: 497-508. 10.1677/erc.1.01209CrossRefPubMed

38.

Mitsutake N, Knauf JA, Mitsutake Shin, Mesa C, Zhang L: Conditional BRAF V600E expression induces DNA synthesis, apoptosis, dedifferentiation and chromosomal instability in thyroid PCCL3 cells. Cancer Res. 2005, 65: 2465-2473. 10.1158/0008-5472.CAN-04-3314CrossRefPubMed

39.

Cahill S, Smyth P, Finn SP, Denning K, Flavin R, O'Regan EM, Li JH, Potratz A, Guenther SM, Henfrey R, O'Leary JJ, Sheils O: Effect of ret/PTC 1 rearrangement on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Mol Cancer. 2006, 5: 70- 10.1186/1476-4598-5-70PubMedCentralCrossRefPubMed

40.

Smyth P, Finn S, Cahill S, O'Regan E, Flavin R, O'Leary JJ, Sheils O: ret/PTC and BRAF act as distinct molecular, time dependent triggers in a sporadic Irish cohort of papillary thyroid carcinoma. Int J Surg Pathol. 2005, 13: 1-8.CrossRefPubMed

41.

Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)). Methods. 2001, 25 (4): 402-8. 10.1006/meth.2001.1262CrossRefPubMed

Title: Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model
Authors: Susanne Cahill
Paul Smyth
Karen Denning
Richard Flavin
Jinghuan Li
Astrid Potratz
Simone M Guenther
Richard Henfrey
John J O'Leary
Orla Sheils
Publication date: 01-12-2007
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2007
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-6-21

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Abstract

Background

Aim

Results

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