BACKGROUND: Better insights into the molecular changes involved in virus-associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV-dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology. METHODS: Fresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection. RESULTS: We defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV-negative keratinocytes. CONCLUSIONS: We identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of clinically relevant diagnostic and/or therapeutic biomarkers for tumors of viral and non-viral etiology.

Department of Genetics and Microbiology Faculty of Science Charles University Prague Prague Czech Republic

Department of Immunology Institute of Hematology and Blood Transfusion U Nemocnice 2094 1 Prague 2 CZ 12820 Czech Republic

Department of Otorhinolaryngology and Head and Neck Surgery 1st Faculty of Medicine Charles University Prague Motol University Hospital Prague Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine Charles University Prague Prague Czech Republic

Molecular Mechanisms and Biomarkers Group International Agency for Research on Cancer Lyon France

Veterans Affairs Healthcare System and Department of Pathology University of Iowa Iowa City IA USA

Zobrazit více v PubMed

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108. doi: 10.3322/canjclin.55.2.74. PubMed DOI

Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol. 2010;11(8):781–9. doi: 10.1016/S1470-2045(10)70017-6. PubMed DOI PMC

Tachezy R, Klozar J, Rubenstein L, Smith E, Salakova M, Smahelova J, et al. Demographic and risk factors in patients with head and neck tumors. J Med Virol. 2009;81(5):878–87. doi: 10.1002/jmv.21470. PubMed DOI

Koslabova E, Hamsikova E, Salakova M, Klozar J, Foltynova E, Salkova E, et al. Markers of HPV infection and survival in patients with head and neck tumors. Int J Cancer. 2013;133(8):1832–9. doi: 10.1002/ijc.28194. PubMed DOI

Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294–301. doi: 10.1200/JCO.2011.36.4596. PubMed DOI PMC

Blomberg M, Nielsen A, Munk C, Kjaer SK. Trends in head and neck cancer incidence in Denmark, 1978–2007: focus on human papillomavirus associated sites. Int J Cancer. 2011;129(3):733–41. doi: 10.1002/ijc.25699. PubMed DOI

Rietbergen MM, Leemans CR, Bloemena E, Heideman DA, Braakhuis BJ, Hesselink AT, et al. Increasing prevalence rates of HPV attributable oropharyngeal squamous cell carcinomas in the Netherlands as assessed by a validated test algorithm. Int J Cancer. 2013;132(7):1565–71. doi: 10.1002/ijc.27821. PubMed DOI

St Guily JL, Jacquard AC, Pretet JL, Haesebaert J, Beby-Defaux A, Clavel C, et al. Human papillomavirus genotype distribution in oropharynx and oral cavity cancer in France--The EDiTH VI study. J Clin Virol. 2011;51(2):100–4. doi: 10.1016/j.jcv.2011.03.003. PubMed DOI

Dayyani F, Etzel CJ, Liu M, Ho CH, Lippman SM, Tsao AS. Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC) Head Neck Oncol. 2010;2:15. doi: 10.1186/1758-3284-2-15. PubMed DOI PMC

Hafkamp HC, Manni JJ, Haesevoets A, Voogd AC, Schepers M, Bot FJ, et al. Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer. 2008;122(12):2656–64. doi: 10.1002/ijc.23458. PubMed DOI

Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97. doi: 10.1016/S0092-8674(04)00045-5. PubMed DOI

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–61. doi: 10.1073/pnas.0510565103. PubMed DOI PMC

Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353(17):1793–801. doi: 10.1056/NEJMoa050995. PubMed DOI

Jay C, Nemunaitis J, Chen P, Fulgham P, Tong AW. miRNA profiling for diagnosis and prognosis of human cancer. DNA Cell Biol. 2007;26(5):293–300. doi: 10.1089/dna.2006.0554. PubMed DOI

Gao G, Gay HA, Chernock RD, Zhang TR, Luo J, Thorstad WL, et al. A microRNA expression signature for the prognosis of oropharyngeal squamous cell carcinoma. Cancer. 2013;119(1):72–80. doi: 10.1002/cncr.27696. PubMed DOI PMC

Wang X, Wang HK, Li Y, Hafner M, Banerjee NS, Tang S, et al. microRNAs are biomarkers of oncogenic human papillomavirus infections. Proc Natl Acad Sci U S A. 2014;111(11):4262–7. doi: 10.1073/pnas.1401430111. PubMed DOI PMC

Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O'Brien C, et al. MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun. 2007;358(1):12–7. doi: 10.1016/j.bbrc.2007.03.201. PubMed DOI

Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, et al. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res. 2010;16(4):1129–39. doi: 10.1158/1078-0432.CCR-09-2166. PubMed DOI

Childs G, Fazzari M, Kung G, Kawachi N, Brandwein-Gensler M, McLemore M, et al. Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol. 2009;174(3):736–45. doi: 10.2353/ajpath.2009.080731. PubMed DOI PMC

Avissar M, Christensen BC, Kelsey KT, Marsit CJ. MicroRNA expression ratio is predictive of head and neck squamous cell carcinoma. Clin Cancer Res. 2009;15(8):2850–5. doi: 10.1158/1078-0432.CCR-08-3131. PubMed DOI PMC

Wald AI, Hoskins EE, Wells SI, Ferris RL, Khan SA. Alteration of microRNA profiles in squamous cell carcinoma of the head and neck cell lines by human papillomavirus. Head Neck. 2011;33(4):504–12. doi: 10.1002/hed.21475. PubMed DOI PMC

Lajer CB, Nielsen FC, Friis-Hansen L, Norrild B, Borup R, Garnaes E, et al. Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study. Br J Cancer. 2011;104(5):830–40. doi: 10.1038/bjc.2011.29. PubMed DOI PMC

Lajer CB, Garnaes E, Friis-Hansen L, Norrild B, Therkildsen MH, Glud M, et al. The role of miRNAs in human papilloma virus (HPV)-associated cancers: bridging between HPV-related head and neck cancer and cervical cancer. Br J Cancer. 2012;106(9):1526–34. doi: 10.1038/bjc.2012.109. PubMed DOI PMC

Rotnaglova E, Tachezy R, Salakova M, Prochazka B, Kosl'abova E, Vesela E, et al. HPV involvement in tonsillar cancer: prognostic significance and clinically relevant markers. Int J Cancer. 2011;129(1):101–10. doi: 10.1002/ijc.25889. PubMed DOI

Vojtechova Z, Sabol I, Salakova M, Turek L, Grega M, Smahelova J, et al. Analysis of the integration of human papillomaviruses in head and neck tumours in relation to patients' prognosis. Int J Cancer. 2016;138(2):386–95. doi: 10.1002/ijc.29712. PubMed DOI

Lace MJ, Anson JR, Klingelhutz AJ, Lee JH, Bossler AD, Haugen TH, et al. Human papillomavirus (HPV) type 18 induces extended growth in primary human cervical, tonsillar, or foreskin keratinocytes more effectively than other high-risk mucosal HPVs. J Virol. 2009;83(22):11784–94. doi: 10.1128/JVI.01370-09. PubMed DOI PMC

Lace MJ, Anson JR, Klussmann JP, Wang DH, Smith EM, Haugen TH, et al. Human papillomavirus type 16 (HPV-16) genomes integrated in head and neck cancers and in HPV-16-immortalized human keratinocyte clones express chimeric virus-cell mRNAs similar to those found in cervical cancers. J Virol. 2011;85(4):1645–54. doi: 10.1128/JVI.02093-10. PubMed DOI PMC

Tachezy R, Smahelova J, Kaspirkova J, Salakova M. Human papillomavirus type-specific prevalence in the cervical cancer screening population of Czech women. PLoS One. 2013;8(11) doi: 10.1371/journal.pone.0079156. PubMed DOI PMC

Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A, Snijders PJ, Pawlita M, et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer. 2007;121(11):2465–72. doi: 10.1002/ijc.22980. PubMed DOI

Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007;110(7):1429–35. doi: 10.1002/cncr.22963. PubMed DOI

Lindquist D, Romanitan M, Hammarstedt L, Nasman A, Dahlstrand H, Lindholm J, et al. Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol Oncol. 2007;1(3):350–5. doi: 10.1016/j.molonc.2007.08.005. PubMed DOI PMC

Chang SS, Jiang WW, Smith I, Poeta LM, Begum S, Glazer C, et al. MicroRNA alterations in head and neck squamous cell carcinoma. Int J Cancer. 2008;123(12):2791–7. doi: 10.1002/ijc.23831. PubMed DOI PMC

Ramdas L, Giri U, Ashorn CL, Coombes KR, El-Naggar A, Ang KK, et al. miRNA expression profiles in head and neck squamous cell carcinoma and adjacent normal tissue. Head Neck. 2009;31(5):642–54. doi: 10.1002/hed.21017. PubMed DOI PMC

Hui AB, Lin A, Xu W, Waldron L, Perez-Ordonez B, Weinreb I, et al. Potentially prognostic miRNAs in HPV-associated oropharyngeal carcinoma. Clin Cancer Res. 2013;19(8):2154–62. doi: 10.1158/1078-0432.CCR-12-3572. PubMed DOI

Miller DL, Davis JW, Taylor KH, Johnson J, Shi Z, Williams R, et al. Identification of a human papillomavirus-associated oncogenic miRNA panel in human oropharyngeal squamous cell carcinoma validated by bioinformatics analysis of the Cancer Genome Atlas. Am J Pathol. 2015;185(3):679–92. doi: 10.1016/j.ajpath.2014.11.018. PubMed DOI PMC

Li J, Li L, Li Z, Gong G, Chen P, Liu H, et al. The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion. Gynecol Oncol. 2015;137(1):125–33. doi: 10.1016/j.ygyno.2015.01.531. PubMed DOI

Li Y, Xu D, Bao C, Zhang Y, Chen D, Zhao F, et al. MicroRNA-135b, a HSF1 target, promotes tumor invasion and metastasis by regulating RECK and EVI5 in hepatocellular carcinoma. Oncotarget. 2015;6(4):2421–33. doi: 10.18632/oncotarget.2965. PubMed DOI PMC

Al-Khalaf HH, Aboussekhra A. MicroRNA-141 and microRNA-146b-5p inhibit the prometastatic mesenchymal characteristics through the RNA-binding protein AUF1 targeting the transcription factor ZEB1 and the protein kinase AKT. J Biol Chem. 2014;289(45):31433–47. doi: 10.1074/jbc.M114.593004. PubMed DOI PMC

Liang HL, Hu AP, Li SL, Xie JP, Ma QZ, Liu JY. MiR-454 prompts cell proliferation of human colorectal cancer cells by repressing CYLD expression. Asian Pac J Cancer Prev. 2015;16(6):2397–402. doi: 10.7314/APJCP.2015.16.6.2397. PubMed DOI

Wang C, Jiang T. MicroRNA-335 represents an independent prognostic marker in cervical cancer. Tumour Biol. 2015;36(8):5825–30. doi: 10.1007/s13277-015-3252-2. PubMed DOI

Scarola M, Schoeftner S, Schneider C, Benetti R. miR-335 directly targets Rb1 (pRb/p105) in a proximal connection to p53-dependent stress response. Cancer Res. 2010;70(17):6925–33. doi: 10.1158/0008-5472.CAN-10-0141. PubMed DOI

Wong TS, Liu XB, Chung-Wai Ho A, Po-Wing Yuen A, Wai-Man Ng R, Ignace WW. Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through microRNA profiling. Int J Cancer. 2008;123(2):251–7. doi: 10.1002/ijc.23583. PubMed DOI

Zheng ZM, Wang X. Regulation of cellular miRNA expression by human papillomaviruses. Biochim Biophys Acta. 2011;1809(11–12):668–77. doi: 10.1016/j.bbagrm.2011.05.005. PubMed DOI PMC

Guan X, Liu Z, Liu H, Yu H, Wang LE, Sturgis EM, et al. A functional variant at the miR-885-5p binding site of CASP3 confers risk of both index and second primary malignancies in patients with head and neck cancer. FASEB J. 2013;27(4):1404–12. doi: 10.1096/fj.12-223420. PubMed DOI PMC

Kinose Y, Sawada K, Nakamura K, Sawada I, Toda A, Nakatsuka E, et al. The hypoxia-related microRNA miR-199a-3p displays tumor suppressor functions in ovarian carcinoma. Oncotarget. 2015;6(13):11342–56. doi: 10.18632/oncotarget.3604. PubMed DOI PMC

Tian R, Xie X, Han J, Luo C, Yong B, Peng H, et al. miR-199a-3p negatively regulates the progression of osteosarcoma through targeting AXL. Am J Cancer Res. 2014;4(6):738–50. PubMed PMC

Nakanishi H, Taccioli C, Palatini J, Fernandez-Cymering C, Cui R, Kim T, et al. Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway. Oncogene. 2014;33(6):702–12. doi: 10.1038/onc.2013.13. PubMed DOI PMC

Henson BJ, Bhattacharjee S, O'Dee DM, Feingold E, Gollin SM. Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to malignancy. Genes Chromosomes Cancer. 2009;48(7):569–82. doi: 10.1002/gcc.20666. PubMed DOI PMC

Nuovo GJ, Wu X, Volinia S, Yan F, di Leva G, Chin N, et al. Strong inverse correlation between microRNA-125b and human papillomavirus DNA in productive infection. Diagn Mol Pathol. 2010;19(3):135–43. doi: 10.1097/PDM.0b013e3181c4daaa. PubMed DOI PMC

Lan D, Zhang X, He R, Tang R, Li P, He Q, et al. MiR-133a is downregulated in non-small cell lung cancer: a study of clinical significance. Eur J Med Res. 2015;20:50. doi: 10.1186/s40001-015-0139-z. PubMed DOI PMC

Song X, Shi B, Huang K, Zhang W. miR-133a inhibits cervical cancer growth by targeting EGFR. Oncol Rep. 2015;34(3):1573–80. PubMed

Gong Y, Ren J, Liu K, Tang LM. Tumor suppressor role of miR-133a in gastric cancer by repressing IGF1R. World J Gastroenterol. 2015;21(10):2949–58. doi: 10.3748/wjg.v21.i10.2949. PubMed DOI PMC

Kinoshita T, Nohata N, Watanabe-Takano H, Yoshino H, Hidaka H, Fujimura L, et al. Actin-related protein 2/3 complex subunit 5 (ARPC5) contributes to cell migration and invasion and is directly regulated by tumor-suppressive microRNA-133a in head and neck squamous cell carcinoma. Int J Oncol. 2012;40(6):1770–8. PubMed

Kinoshita T, Nohata N, Fuse M, Hanazawa T, Kikkawa N, Fujimura L, et al. Tumor suppressive microRNA-133a regulates novel targets: moesin contributes to cancer cell proliferation and invasion in head and neck squamous cell carcinoma. Biochem Biophys Res Commun. 2012;418(2):378–83. doi: 10.1016/j.bbrc.2012.01.030. PubMed DOI

Wang F, Ren X, Zhang X. Role of microRNA-150 in solid tumors. Oncol Lett. 2015;10(1):11–6. PubMed PMC

Formosa A, Markert EK, Lena AM, Italiano D, Finazzi-Agro' E, Levine AJ, et al. MicroRNAs, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. Oncogene. 2014;33(44):5173–82. doi: 10.1038/onc.2013.451. PubMed DOI

Re M, Ceka A, Rubini C, Ferrante L, Zizzi A, Gioacchini FM, et al. MicroRNA-34c-5p is related to recurrence in laryngeal squamous cell carcinoma. Laryngoscope. 2015;125(9):E306–12. doi: 10.1002/lary.25475. PubMed DOI

Wu Z, Wu Y, Tian Y, Sun X, Liu J, Ren H, et al. Differential effects of miR-34c-3p and miR-34c-5p on the proliferation, apoptosis and invasion of glioma cells. Oncol Lett. 2013;6(5):1447–52. PubMed PMC

Tao K, Yang J, Guo Z, Hu Y, Sheng H, Gao H, et al. Prognostic value of miR-221-3p, miR-342-3p and miR-491-5p expression in colon cancer. Am J Transl Res. 2014;6(4):391–401. PubMed PMC

Ergun S, Tayeb TS, Arslan A, Temiz E, Arman K, Safdar M, et al. The investigation of miR-221-3p and PAK1 gene expressions in breast cancer cell lines. Gene. 2015;555(2):377–81. doi: 10.1016/j.gene.2014.11.036. PubMed DOI

Zhu L, Chen H, Zhou D, Li D, Bai R, Zheng S, et al. MicroRNA-9 up-regulation is involved in colorectal cancer metastasis via promoting cell motility. Med Oncol. 2012;29(2):1037–43. doi: 10.1007/s12032-011-9975-z. PubMed DOI

Liu W, Gao G, Hu X, Wang Y, Schwarz JK, Chen JJ, et al. Activation of miR-9 by human papillomavirus in cervical cancer. Oncotarget. 2014;5(22):11620–30. doi: 10.18632/oncotarget.2599. PubMed DOI PMC

Myklebust MP, Bruland O, Fluge O, Skarstein A, Balteskard L, Dahl O. MicroRNA-15b is induced with E2F-controlled genes in HPV-related cancer. Br J Cancer. 2011;105(11):1719–25. doi: 10.1038/bjc.2011.457. PubMed DOI PMC

Rao Q, Shen Q, Zhou H, Peng Y, Li J, Lin Z. Aberrant microRNA expression in human cervical carcinomas. Med Oncol. 2012;29(2):1242–8. doi: 10.1007/s12032-011-9830-2. PubMed DOI

Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10(5):593–601. doi: 10.1038/ncb1722. PubMed DOI

Zhu K, Pan Q, Jia LQ, Dai Z, Ke AW, Zeng HY, et al. MiR-302c inhibits tumor growth of hepatocellular carcinoma by suppressing the endothelial-mesenchymal transition of endothelial cells. Sci Rep. 2014;4:5524. PubMed PMC

Xiong H, Li Q, Liu S, Wang F, Xiong Z, Chen J, et al. Integrated microRNA and mRNA transcriptome sequencing reveals the potential roles of miRNAs in stage I endometrioid endometrial carcinoma. PLoS One. 2014;9(10) doi: 10.1371/journal.pone.0110163. PubMed DOI PMC

Xu XT, Xu Q, Tong JL, Zhu MM, Nie F, Chen X, et al. MicroRNA expression profiling identifies miR-328 regulates cancer stem cell-like SP cells in colorectal cancer. Br J Cancer. 2012;106(7):1320–30. doi: 10.1038/bjc.2012.88. PubMed DOI PMC

Xu J, Ai Q, Cao H, Liu Q. MiR-185-3p and miR-324-3p predict radiosensitivity of nasopharyngeal carcinoma and modulate cancer cell growth and apoptosis by targeting SMAD7. Med Sci Monit. 2015;21:2828–36. doi: 10.12659/MSM.895660. PubMed DOI PMC

Baba O, Hasegawa S, Nagai H, Uchida F, Yamatoji M, Kanno NI, et al. MicroRNA-155-5p is associated with oral squamous cell carcinoma metastasis and poor prognosis. J Oral Pathol Med. 2015 PubMed

Jamali Z, Asl Aminabadi N, Attaran R, Pournagiazar F, Ghertasi Oskouei S, Ahmadpour F. MicroRNAs as prognostic molecular signatures in human head and neck squamous cell carcinoma: a systematic review and meta-analysis. Oral Oncol. 2015;51(4):321–31. doi: 10.1016/j.oraloncology.2015.01.008. PubMed DOI

Lin RJ, Xiao DW, Liao LD, Chen T, Xie ZF, Huang WZ, et al. MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma. J Surg Oncol. 2012;105(2):175–82. doi: 10.1002/jso.22066. PubMed DOI

Bufalino A, Cervigne NK, de Oliveira CE, Fonseca FP, Rodrigues PC, Macedo CC, et al. Low miR-143/miR-145 cluster levels induce activin a overexpression in oral squamous cell carcinomas, which contributes to poor prognosis. PLoS One. 2015;10(8) doi: 10.1371/journal.pone.0136599. PubMed DOI PMC

Lack of Conserved miRNA Deregulation in HPV-Induced Squamous Cell Carcinomas

Genome-wide miRNA profiling reinforces the importance of miR-9 in human papillomavirus associated oral and oropharyngeal head and neck cancer

The Role of miRNAs in Virus-Mediated Oncogenesis

Comparison of the miRNA expression profiles in fresh frozen and formalin-fixed paraffin-embedded tonsillar tumors