New miRNA expression abnormalities in laryngeal squamous cell carcinoma
Abstract
BACKGROUND:
Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers - and so remain the focus of extensive investigation in laryngeal cancer.
OBJECTIVE:
We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers.
METHODS:
We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile.
RESULTS:
While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated.
CONCLUSIONS:
The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.
References
[1] | Afanasyeva E.A., , Mestdagh P., , Kumps C., , Vandesompele J., , Ehemann V., , Theissen J., , Fischer M., , Zapatka M., , Brors B., , Savelyeva L., , Sagulenko V., , Speleman F., , Schwab M., and Westermann F., MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival, Cell Death Differ 18: ((2011) ), 974-84. |
[2] | Cizkova M., , Vacher S., , Meseure D., , Trassard M., , Susini A., , Mlcuchova D., , Callens C., , Rouleau E., , Spyratos F., , Lidereau R., and Bieche I., PIK3R1 underexpression is an independent prognostic marker in breast cancer, BMC Cancer 13: ((2013) ), 545. |
[3] | Coskunpinar E., , Oltulu Y.M., , Orhan K.S., , Tiryakioglu N.O., , Kanliada D., and Akbas F., Identification of a differential expression signature associated with tumorigenesis and metastasis of laryngeal carcinoma, Gene 534: ((2014) ), 183-8. |
[4] | Diaz Prado S.M., , Medina Villaamil V., , Aparicio Gallego G., , Blanco Calvo M., , Lopez Cedrun J.L., , Sironvalle Soliva S., , Valladares Ayerbes M., , Garcia Campelo R., and Anton Aparicio L.M., Expression of Wnt gene family and frizzled receptors in head and neck squamous cell carcinomas, Virchows Arch 455: ((2009) ), 67-75. |
[5] | Feller S.M., Crk family adaptors-signalling complex formation and biological roles, Oncogene 20: ((2001) ), 6348-71. |
[6] | Formosa A., , Markert E.K., , Lena A.M., , Italiano D., , Finazzi-Agro E., , Levine A.J., , Bernardini S., , Garabadgiu A.V., , Melino G., and Candi E., 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 33: ((2014) ), 5173-82. |
[7] | Galera-Ruiz H., , Rios-Moreno M.J., , Gonzalez-Campora R., , Ortega I., , Fernandez A., , Garcia-Escudero A., and Galera-Davidson H., The cadherin-catenin complex in laryngeal squamous cell carcinoma, Eur Arch Otorhinolaryngol 269: ((2012) ), 1183-8. |
[8] | Ganci F., , Sacconi A., , Bossel Ben-Moshe N., , Manciocco V., , Sperduti I., , Strigari L., , Covello R., , Benevolo M., , Pescarmona E., , Domany E., , Muti P., , Strano S., , Spriano G., , Fontemaggi G., and Blandino G., Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients, Ann Oncol 24: ((2013) ), 3082-8. |
[9] | Goka E.T., and Lippman M.E., Loss of the E3 ubiquitin ligase HACE1 results in enhanced Rac1 signaling contributing to breast cancer progression, Oncogene ((2015) ). |
[10] | Gupta S., , Iljin K., , Sara H., , Mpindi J.P., , Mirtti T., , Vainio P., , Rantala J., , Alanen K., , Nees M., and Kallioniemi O., FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells, Cancer Res 70: ((2010) ), 6735-45. |
[11] | Heneghan H.M., , Miller N., and Kerin M.J., MiRNAs as biomarkers and therapeutic targets in cancer, Curr Opin Pharmacol 10: ((2010) ), 543-50. |
[12] | Hu A., , Huang J.J., , Xu W.H., , Jin X.J., , Li J.P., , Tang Y.J., , Huang X.F., , Cui H.J., and Sun G.B., miR-21 and miR-375 microRNAs as candidate diagnostic biomarkers in squamous cell carcinoma of the larynx: association with patient survival, Am J Transl Res 6: ((2014) ), 604-13. |
[13] | Hur K., , Toiyama Y., , Schetter A.J., , Okugawa Y., , Harris C.C., , Boland C.R., and Goel A., Identification of a metastasis-specific MicroRNA signature in human colorectal cancer, J Natl Cancer Inst 107: ((2015) ). |
[14] | Jaiswal B.S., , Janakiraman V., , Kljavin N.M., , Chaudhuri S., , Stern H.M., , Wang W., , Kan Z., , Dbouk H.A., , Peters B.A., , Waring P., , Dela Vega T., , Kenski D.M., , Bowman K.K., , Lorenzo M., , Li H., , Wu J., , Modrusan Z., , Stinson J., , Eby M., , Yue P., , Kaminker J.S., , de Sauvage F.J., , Backer J.M., and Seshagiri S., Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation, Cancer Cell 16: ((2009) ), 463-74. |
[15] | Jenckel F., and Knecht R., State of the art in the treatment of laryngeal cancer, Anticancer Res 33: ((2013) ), 4701-10. |
[16] | Joseph A.W., and D'Souza G., Epidemiology of human papillomavirus-related head and neck cancer, Otolaryngol Clin North Am 45: ((2012) ), 739-64. |
[17] | Kucuk C., , Hu X., , Iqbal J., , Gaulard P., , Klinkebiel D., , Cornish A., , Dave B.J., and Chan W.C., HACE1 is a tumor suppressor gene candidate in natural killer cell neoplasms, Am J Pathol 182: ((2013) ), 49-55. |
[18] | Kumar S., , Fajardo J.E., , Birge R.B., and Sriram G., Crk at the quarter century mark: perspectives in signaling and cancer, J Cell Biochem 115: ((2014) ), 819-25. |
[19] | Lin M., , Chen W., , Huang J., , Gao H., , Ye Y., , Song Z., and Shen X., MicroRNA expression profiles in human colorectal cancers with liver metastases, Oncol Rep 25: ((2011) ), 739-47. |
[20] | Lu Z.M., , Lin Y.F., , Jiang L., , Chen L.S., , Luo X.N., , Song X.H., , Chen S.H., and Zhang S.Y., Micro-ribonucleic acid expression profiling and bioinformatic target gene analyses in laryngeal carcinoma, Onco Targets Ther 7: ((2014) ), 525-33. |
[21] | Lui V.W., , Hedberg M.L., , Li H., , Vangara B.S., , Pendleton K., , Zeng Y., , Lu Y., , Zhang Q., , Du Y., , Gilbert B.R., , Freilino M., , Sauerwein S., , Peyser N.D., , Xiao D., , Diergaarde B., , Wang L., , Chiosea S., , Seethala R., , Johnson J.T., , Kim S., , Duvvuri U., , Ferris R.L., , Romkes M., , Nukui T., , Kwok-Shing Ng P., , Garraway L.A., , Hammerman P.S., , Mills G.B., and Grandis J.R., Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers, Cancer Discov 3: ((2013) ), 761-9. |
[22] | Luo H.N., , Wang Z.H., , Sheng Y., , Zhang Q., , Yan J., , Hou J., , Zhu K., , Cheng Y., , Xu Y.L., , Zhang X.H., , Xu M., and Ren X.Y., MiR-139 targets CXCR4 and inhibits the proliferation and metastasis of laryngeal squamous carcinoma cells, Med Oncol 31: ((2014) ), 789. |
[23] | Machiels J.P., , Lambrecht M., , Hanin F.X., , Duprez T., , Gregoire V., , Schmitz S., and Hamoir M., Advances in the management of squamous cell carcinoma of the head and neck, F1000Prime Rep 6: ((2014) ), 44. |
[24] | Makitie A.A., and Monni O., Molecular profiling of laryngeal cancer, Expert Rev Anticancer Ther 9: ((2009) ), 1251-60. |
[25] | Mellor P., , Furber L.A., , Nyarko J.N., and Anderson D.H., Multiple roles for the p85alpha isoform in the regulation and function of PI3K signalling and receptor trafficking, Biochem J 441: ((2012) ), 23-37. |
[26] | Miller C.T., , Chen G., , Gharib T.G., , Wang H., , Thomas D.G., , Misek D.E., , Giordano T.J., , Yee J., , Orringer M.B., , Hanash S.M., and Beer D.G., Increased C-CRK proto-oncogene expression is associated with an aggressive phenotype in lung adenocarcinomas, Oncogene 22: ((2003) ), 7950-7. |
[27] | Ni R.S., , Shen X., , Qian X., , Yu C., , Wu H., and Gao X., Detection of differentially expressed genes and association with clinicopathological features in laryngeal squamous cell carcinoma, Oncol Lett 4: ((2012) ), 1354-1360. |
[28] | Niehrs C., The complex world of WNT receptor signalling, Nat Rev Mol Cell Biol 13: ((2012) ), 767-79. |
[29] | Pang F., , Zha R., , Zhao Y., , Wang Q., , Chen D., , Zhang Z., , Chen T., , Yao M., , Gu J., and He X., MiR-525-3p enhances the migration and invasion of liver cancer cells by downregulating ZNF395, PLoS One 9: ((2014) ), e90867. |
[30] | Perez-Ordonez B., , Beauchemin M., and Jordan R.C., Molecular biology of squamous cell carcinoma of the head and neck, J Clin Pathol 59: ((2006) ), 445-53. |
[31] | Psyrri A., , Kotoula V., , Fountzilas E., , Alexopoulou Z., , Bobos M., , Televantou D., , Karayannopoulou G., , Krikelis D., , Markou K., , Karasmanis I., , Angouridakis N., , Kalogeras K.T., , Nikolaou A., and Fountzilas G., Prognostic significance of the Wnt pathway in squamous cell laryngeal cancer, Oral Oncol 50: ((2014) ), 298-305. |
[32] | Ramroth H., , Schoeps A., , Rudolph E., , Dyckhoff G., , Plinkert P., , Lippert B., , Feist K., , Delank K.W., , Scheuermann K., , Baier G., , Ott I., , Chenouda S., , Becher H., and Dietz A., Factors predicting survival after diagnosis of laryngeal cancer, Oral Oncol 47: ((2011) ), 1154-8. |
[33] | Ren J., , Zhu D., , Liu M., , Sun Y., and Tian L., Downregulation of miR-21 modulates Ras expression to promote apoptosis and suppress invasion of Laryngeal squamous cell carcinoma, Eur J Cancer 46: ((2010) ), 3409-16. |
[34] | Sakata M., , Kitamura Y.H., , Sakuraba K., , Goto T., , Mizukami H., , Saito M., , Ishibashi K., , Kigawa G., , Nemoto H., , Sanada Y., and Hibi K., Methylation of HACE1 in gastric carcinoma, Anticancer Res 29: ((2009) ), 2231-3. |
[35] | Shen K., , Liang Q., , Xu K., , Cui D., , Jiang L., , Yin P., , Lu Y., , Li Q., and Liu J., MiR-139 inhibits invasion and metastasis of colorectal cancer by targeting the type I insulin-like growth factor receptor, Biochem Pharmacol 84: ((2012) ), 320-30. |
[36] | Slaby O., , Bienertova-Vasku J., , Svoboda M., and Vyzula R., Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer, J Cell Mol Med 16: ((2012) ), 8-21. |
[37] | Sun X., , Song Y., , Tai X., , Liu B., and Ji W., MicroRNA expression and its detection in human supraglottic laryngeal squamous cell carcinoma, Biomed Rep 1: ((2013) ), 743-746. |
[38] | Tan C.T., , Chu C.Y., , Lu Y.C., , Chang C.C., , Lin B.R., , Wu H.H., , Liu H.L., , Cha S.T., , Prakash E., , Ko J.Y., and Kuo M.L., CXCL12/CXCR4 promotes laryngeal and hypopharyngeal squamous cell carcinoma metastasis through MMP-13-dependent invasion via the ERK1/2/AP-1 pathway, Carcinogenesis 29: ((2008) ), 1519-27. |
[39] | Tickenbrock L., , Hehn S., , Sargin B., , Choudhary C., , Baumer N., , Buerger H., , Schulte B., , Muller O., , Berdel W.E., , Muller-Tidow C., and Serve H., Activation of Wnt signalling in acute myeloid leukemia by induction of Frizzled-4, Int J Oncol 33: ((2008) ), 1215-21. |
[40] | Torrente M.C., , Rodrigo J.P., , Haigentz, Jr. M., , Dikkers F.G., , Rinaldo A., , Takes R.P., , Olofsson J., and Ferlito A., Human papillomavirus infections in laryngeal cancer, Head Neck 33: ((2011) ), 581-6. |
[41] | Weitzenfeld P., and Ben-Baruch A., The chemokine system, and its CCR5 and CXCR4 receptors, as potential targets for personalized therapy in cancer, Cancer Lett 352: ((2014) ), 36-53. |
[42] | Wojcicka A., , de la Chapelle A., and Jazdzewski K., MicroRNA-related sequence variations in human cancers, Hum Genet 133: ((2014) ), 463-9. |
[43] | Yao D., , Dai C., and Peng S., Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation, Mol Cancer Res 9: ((2011) ), 1608-20. |
[44] | Zhang H.D., , Jiang L.H., , Sun D.W., , Li J., and Tang J.H., MiR-139-5p: promising biomarker for cancer, Tumour Biol 36: ((2015) ), 1355-65. |
