MicroRNAs as molecular markers in lung cancer
Lung cancer is the most common cause of cancer death in the western world for both men and women. Lung cancer appears to be a perfect candidate for a screening program, since it is the number one cancer killer, it has a long preclinical phase, curative treatment for the minority of patients who are diagnosed early and a target population at risk (smokers) and it is also a major economic burden. The earliest approaches to identifying cancer markers were based on preliminary clinical or pathological observations, although molecular biology is a strong candidate for occupying a place among the set of methods. In search of markers, several alterations, such as mutations, loss of heterozygosity, microsatellite instability, DNA methylation, mitochondrial DNA mutations, viral DNA, modified expression of mRNA, miRNA and proteins, and structurally altered proteins have all been analysed. MicroRNAs (miRNA) are small RNA molecules, about 19-25 nucleotides long and encoded in genomes of plants, animals, fungi and viruses. It has been reported that miRNAs may have multiple functions in lung development and that aberrant expression of miRNAs could induce lung tumorigenesis. We review here the role of miRNAs in lung tumorigenesis and also as a novel type of biomarker.
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Silva J, Garcia V, Lopez-Gonzalez A, Provencio M. MicroRNAs as molecular markers in lung cancer. Int J Cancer Ther Oncol 2013;1(1):010111.
Risch A, Plass C. Lung cancer epigenetics and genetics. Int J Cancer 2008; 123: 1-7.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics. CA Cancer J Clin 2008; 58:71-96.
Girard L, Zöchbauer-Müller S, Virmani AK, Gazdar AF, Minna JD. Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and on-small cell lung cancer, and loci clustering. Cancer Res 2000; 60:4894-906.
Cooper S, Spiro SG. Small cell lung cancer: treatment review. Respirology 2006; 11: 241-8.
Khuder SA. Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis. Lung Cancer 2001; 31:139-48.
Mattson ME, Pollack ES, Cullen JW. What are the odds that smoking will kill you? Am J Public Health 1987; 77:425-31.
Schwartz AG, Prysak GM, Bock CH, Cote ML. The molecular epidemiology of lung cancer. Carcinogenesis 2007, 28:507-18.
Wakelee HA, Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, Holmberg L, Yong LC, Kolonel LN, Gould MK, West DW. Lung cancer incidence in never smokers. J Clin Oncol 2007; 25:472-8.
Smith RA, Cokkinides V, Eyre HJ. Cancer screening in the United States, 2007: a review of current guidelines, practices, and prospects. CA Cancer J Clin 2007, 57:90-104.
Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med 2004; 350:379-92.
International Early Lung Cancer Action Program Investigators, Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006; 355:1763-71.
Markowitz SB, Miller A, Miller J, Manowitz A, Kieding S, Sider L, Morabia A. Ability of low-dose helical CT to distinguish between benign and malignant noncalcified lung nodules. Chest 2007; 131:1028-34.
Sidransky D. Emerging molecular markers of cancer. Nat Rev Cancer 2002; 2:210-9.
Salgia R, Skarin AT. Molecular abnormalities in lung cancer. J Clin Oncol 1998; 16:1207-17.
Daigo Y, Nishiwaki T, Kawasoe T, Tamari M, Tsuchiya E, Nakamura Y. Molecular cloning of a candidate tumor suppressor gene, DLC1, from chromosome 3p21.3. Cancer Res 1999; 59:1966-72.
Benson AB 3rd, Choti MA, Cohen AM, Doroshow JH, Fuchs C, Kiel K, Martin EW Jr, McGinn C, Petrelli NJ, Posey JA, Skibber JM, Venook A, Yeatman TJ; National Comprehensive Cancer Network. NCCN Practice Guidelines for Colorectal Cancer. Oncology (Williston Park) 2000; 14:203-12.
Feneley MR, Partin AW. Diagnosis of localized prostate cancer: 10 years of progress. Curr Opin Urol 2000; 10:319-27.
Harris LN, Liotcheva V, Broadwater G, Ramirez MJ, Maimonis P, Anderson S, Everett T, Harpole D, Moore MB, Berry DA, Rizzeri D, Vredenburgh JJ, Bentley RC. Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy. J Clin Oncol 2001; 19:1698-706.
Rosell R, Morán T, Carcereny E, Quiroga V, Molina MA, Costa C, Benlloch S, Tarón M. Non-small-cell lung cancer harbouring mutations in the EGFR kinase domain. Clin Transl Oncol 2010; 12:75-80.
Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC; IALT Bio Investigators. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006; 355:983-91.
Matzke M, Matzke AJ, Kooter JM. RNA: guiding gene silencing. Science 2001; 293:1080-3.
Ambros V. The functions of animal microRNAs. Nature 2004; 431:350-5.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116:281-97.
Williams AE, Moschos SA, Perry MM, Barnes PJ, Lindsay MA. Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev Dyn 2007; 236:572-80.
Lü J, Qian J, Chen F, Tang X, Li C, Cardoso WV. Differential expression of components of the microRNA machinery during mouse organogenesis. Biochem Biophys Res Commun. 2005; 334:319-23.
Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Müller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000; 408:86-9.
Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G. Numerous microRNPs in neuronal cells containing novel microRNAs. RNA 2003; 9:180-6.
Ishizuka A, Siomi MC, Siomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev 2002; 16:2497-508.
Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N. Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region. Biochem Biophys Res Commun 2003; 304:184-90.
Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006; 6:259-69.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006; 6:857-66.
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.
Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005; 353:1793-801.
Lu Y, Okubo T, Rawlins E, Hogan BL. Epithelial progenitor cells of the embryonic lung and the role of microRNAs in their proliferation. Proc Am Thorac Soc 2008; 5:300-4.
Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, Wilson M, Wang X, Shelton J, Shingara J, Chin L, Brown D, Slack FJ. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 2007; 67:7713-22.
Zhang B, Pan X, Cobb GP, Anderson TA. MicroRNAs as oncogenes and tumor suppressors. Dev Biol 2007; 302:1-12.
Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene. 2006, 25(46):6188-96.
Field RW, Smith BJ, Platz CE, Robinson RA, Neuberger JS, Brus CP, Lynch CF. Lung cancer histologic type in the surveillance, epidemiology, and end results registry versus independent review. J Natl Cancer Inst 2004; 96:1105-7.
Stang A, Pohlabeln H, Müller KM, Jahn I, Giersiepen K, Jöckel KH. Diagnostic agreement in the histopathological evaluation of lung cancer tissue in a population-based case-control study. Lung Cancer 2006; 52:29-36.
Fabbri M, Garzon R, Cimmino A, Liu Z, Zanesi N, Callegari E, Liu S, Alder H, Costinean S, Fernandez-Cymering C, Volinia S, Guler G, Morrison CD, Chan KK, Marcucci G, Calin GA, Huebner K, Croce CM. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci U S A 2007; 104:15805-10.
Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004; 64:3753-6.
Inamura K, Togashi Y, Nomura K, Ninomiya H, Hiramatsu M, Satoh Y, Okumura S, Nakagawa K, Ishikawa Y. let-7 microRNA expression is reduced in bronchioloalveolar carcinoma, a non-invasive carcinoma, and is not correlated with prognosis. Lung Cancer 2007; 58:392-6.
Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, Cheng CL, Yu CJ, Lee YC, Chen HS, Su TJ, Chiang CC, Li HN, Hong QS, Su HY, Chen CC, Chen WJ, Liu CC, Chan WK, Chen WJ, Li KC, Chen JJ, Yang PC. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 2008; 13:48-57.
Fazi F, Fontemaggi G .MicroRNAs and Lymph Node Metastatic Disease in Lung Cancer. Thorac Surg Clin 2012; 22:167-75.
Wang YS, Wang YH, Xia HP, Zhou SW, Schmid-Bindert G, Zhou CC MicroRNA-214 Regulates the Acquired Resistance to Gefitinib via the PTEN/AKT Pathway in EGFR-mutant Cell Lines. Asian Pac J Cancer Prev 2012; 13:255-60.
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18:997-1006.
García JM, García V, Peña C, Domínguez G, Silva J, Diaz R, Espinosa P, Citores MJ, Collado M, Bonilla F. Extracellular plasma RNA from colon cancer patients is confined in a vesicle-like structure and is mRNA-enriched. RNA 2008; 14:1424-32.
Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer 2009; 10:42-6.
Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS, Hatton CS, Harris AL. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol 2008; 141:672-5.
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008; 105:10513-8.
Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, Poon TC, Ng SS, Sung JJ. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009; 58:1375-81.
Zhu W, Qin W, Atasoy U, Sauter ER. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes 2009; 2:89.
Taylor DD, Gerçel-Taylor C. Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects. Br J Cancer 2005; 92:305-11.
Lodes MJ, Caraballo M, Suciu D, Munro S, Kumar A, Anderson B. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One 2009; 4:e6229.
Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, Chen Y, Xu L, Zen K, Zhang C, Shen H. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol 2010; 28:1721-6.
Hennessey PT, Sanford T, Choudhary A, Mydlarz WW, Brown D, Adai AT, Ochs MF, Ahrendt SA, Mambo E, Califano JA. Serum microRNA biomarkers for detection of non-small cell lung cancer. PLoS One 2012; 7:e32307.
Bianchi F, Nicassio F, Veronesi G, di Fiore P. Circulating microRNAs: next-generation biomarkers for early lung cancer detection. Ecancermedicalscience 2012; 6:246.
Shen J, Todd NW, Zhang H, Yu L, Lingxiao X, Mei Y, Guarnera M, Liao J, Chou A, Lu CL, Jiang Z, Fang H, Katz RL, Jiang F. Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab Invest 2011; 91:579-87.
Rani S, Gately K, Crown J, O'Byrne K, O'Driscoll L. Global analysis of serum microRNAs as potential biomarkers for lung adenocarcinoma. Cancer Biol Ther 2013; 14.
Xu T, Liu X, Han L, Shen H, Liu L, Shu Y. Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer. Clin Transl Oncol 2013.
Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, Yamada H, Suzuki M, Nagino M, Nimura Y, Osada H, Takahashi T. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene 2007; 26:6099-105.
Tavazoie SF, Alarcón C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massagué J. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008; 451:147-52.
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