You are viewing a javascript disabled version of the site. Please enable Javascript for this site to function properly.
Go to headerGo to navigationGo to searchGo to contentsGo to footer
In content section. Select this link to jump to navigation

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.