Potential Role of MiR-9 and MiR-223 in Recurrent Ovarian Cancer

Overview

Journal Mol Cancer

Publisher Biomed Central

Specialties Molecular Biology
Oncology

Date 2008 Apr 30

PMID 18442408

Citations 159

Authors

Alexandros Laios

Sharon OToole

Richard Flavin

Cara Martin

Lynn Kelly

Martina Ring

Stephen P Finn

Ciara Barrett

Massimo Loda

Noreen Gleeson

Tom DArcy

Eamonn McGuinness

Orla Sheils

Brian Sheppard

John O Leary

Affiliations

Soon will be listed here.

Abstract

Background: MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression by binding to target mRNAs. miRNAs have not been comprehensively studied in recurrent ovarian cancer, yet an incurable disease.

Results: Using real-time RT-PCR, we obtained distinct miRNA expression profiles between primary and recurrent serous papillary ovarian adenocarcinomas (n = 6) in a subset of samples previously used in a transcriptome approach. Expression levels of top dysregulated miRNA genes, miR-223 and miR-9, were examined using TaqMan PCR in independent cohorts of fresh frozen (n = 18) and FFPE serous ovarian tumours (n = 22). Concordance was observed on TaqMan analysis for miR-223 and miR-9 between the training cohort and the independent test cohorts. Target prediction analysis for the above miRNA "recurrent metastatic signature" identified genes previously validated in our transcriptome study. Common biological pathways well characterised in ovarian cancer were shared by miR-9 and miR-223 lists of predicted target genes. We provide strong evidence that miR-9 acts as a putative tumour suppressor gene in recurrent ovarian cancer. Components of the miRNA processing machinery, such as Dicer and Drosha are not responsible for miRNA deregulation in recurrent ovarian cancer, as deluded by TaqMan and immunohistochemistry.

Conclusion: We propose a miRNA model for the molecular pathogenesis of recurrent ovarian cancer. Some of the differentially deregulated miRNAs identified correlate with our previous transcriptome findings. Based on integrated transcriptome and miRNA analysis, miR-9 and miR-223 can be of potential importance as biomarkers in recurrent ovarian cancer.

Citing Articles

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MiR-223-3p in Cancer Development and Cancer Drug Resistance: Same Coin, Different Faces.

Barbagallo D, Ponti D, Bassani B, Bruno A, Pulze L, Akkihal S Int J Mol Sci. 2024; 25(15).

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References

Hutvagner G, Simard M . Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol. 2007; 9(1):22-32. DOI: 10.1038/nrm2321. View

Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis M, Nervi C . A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell. 2005; 123(5):819-31. DOI: 10.1016/j.cell.2005.09.023. View

Montenegro D, Romero R, Pineles B, Tarca A, Kim Y, Draghici S . Differential expression of microRNAs with progression of gestation and inflammation in the human chorioamniotic membranes. Am J Obstet Gynecol. 2007; 197(3):289.e1-6. PMC: 2810125. DOI: 10.1016/j.ajog.2007.06.027. View

Zhang L, Huang J, Yang N, Greshock J, Megraw M, Giannakakis A . microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A. 2006; 103(24):9136-41. PMC: 1474008. DOI: 10.1073/pnas.0508889103. View

Megraw M, Sethupathy P, Corda B, Hatzigeorgiou A . miRGen: a database for the study of animal microRNA genomic organization and function. Nucleic Acids Res. 2006; 35(Database issue):D149-55. PMC: 1669779. DOI: 10.1093/nar/gkl904. View

Volinia S, Calin G, Liu C, Ambs S, Cimmino A, Petrocca F . A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006; 103(7):2257-61. PMC: 1413718. DOI: 10.1073/pnas.0510565103. View

Cahill S, Smyth P, Denning K, Flavin R, Li J, Potratz A . Effect of BRAFV600E mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model. Mol Cancer. 2007; 6:21. PMC: 1831483. DOI: 10.1186/1476-4598-6-21. View

Calin G, Croce C . MicroRNA-cancer connection: the beginning of a new tale. Cancer Res. 2006; 66(15):7390-4. DOI: 10.1158/0008-5472.CAN-06-0800. View

Cho R, Campbell M . Transcription, genomes, function. Trends Genet. 2000; 16(9):409-15. DOI: 10.1016/s0168-9525(00)02065-5. View

10.

Lu J, Getz G, Miska E, Alvarez-Saavedra E, Lamb J, Peck D . MicroRNA expression profiles classify human cancers. Nature. 2005; 435(7043):834-8. DOI: 10.1038/nature03702. View

11.

Chendrimada T, Finn K, Ji X, Baillat D, Gregory R, Liebhaber S . MicroRNA silencing through RISC recruitment of eIF6. Nature. 2007; 447(7146):823-8. DOI: 10.1038/nature05841. View

12.

Barad O, Meiri E, Avniel A, Aharonov R, Barzilai A, Bentwich I . MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res. 2004; 14(12):2486-94. PMC: 534673. DOI: 10.1101/gr.2845604. View

13.

Nelson P, Baldwin D, Marie Scearce L, Oberholtzer J, Tobias J, Mourelatos Z . Microarray-based, high-throughput gene expression profiling of microRNAs. Nat Methods. 2005; 1(2):155-61. DOI: 10.1038/nmeth717. View

14.

Eis P, Tam W, Sun L, Chadburn A, Li Z, Gomez M . Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005; 102(10):3627-32. PMC: 552785. DOI: 10.1073/pnas.0500613102. View

15.

Iorio M, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S . MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65(16):7065-70. DOI: 10.1158/0008-5472.CAN-05-1783. View

16.

Ramkissoon S, Mainwaring L, Ogasawara Y, Keyvanfar K, McCoy Jr J, Sloand E . Hematopoietic-specific microRNA expression in human cells. Leuk Res. 2005; 30(5):643-7. DOI: 10.1016/j.leukres.2005.09.001. View

17.

Yang H, Kong W, He L, Zhao J, ODonnell J, Wang J . MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 2008; 68(2):425-33. DOI: 10.1158/0008-5472.CAN-07-2488. View

18.

Kikkawa F, Nawa A, Ino K, Shibata K, Kajiyama H, Nomura S . Advances in treatment of epithelial ovarian cancer. Nagoya J Med Sci. 2006; 68(1-2):19-26. View

19.

Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall J, Harrington K . Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 2007; 9(12):1392-400. DOI: 10.1038/ncb1658. View

20.

Kuehbacher A, Urbich C, Dimmeler S . Targeting microRNA expression to regulate angiogenesis. Trends Pharmacol Sci. 2007; 29(1):12-5. DOI: 10.1016/j.tips.2007.10.014. View