Expression of miR-373 and its predicted target genes E-cadherin and CD44 in patients with laryngeal squamous cell carcinoma

í–zlem Timirci-Kahraman; Ayşegül Verim; Ammad Ahmad Farooqi; Saime Turan; Nazli Ezgi í–zkan-Küçük; ć°lhan Yaylim

doi:10.14715/10.14715/cmb/2017.63.12.8

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Vol. 63 No. 12: Issue 12

Issue Published : December 19, 2017

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Expression of miR-373 and its predicted target genes E-cadherin and CD44 in patients with laryngeal squamous cell carcinoma

https://doi.org/10.14715/10.14715/cmb/2017.63.12.8

í–zlem Timirci-Kahraman

Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

Ayşegül Verim

Department of Otorhinolaryngology/Head and Neck Surgery, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey

Ammad Ahmad Farooqi

Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan

Saime Turan

Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

Nazli Ezgi í–zkan-Küçük

Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

ć°lhan Yaylim

Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

Corresponding Author(s) : ć°lhan Yaylim

ilhanyaylim@gmail.com

Cellular and Molecular Biology, Vol. 63 No. 12: Issue 12
Article Published : December 30, 2017

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a genomically complex disease that is difficult to target, and efforts have been made to identify new treatment strategies and molecular markers that might stratify patients and individualize options for treatment. miR-373 has diametrically opposed roles in different stages and types of cancers. miR-373 has been suggested to quantitatively control E-cadherin and CD44 expression. We studied the expression of miR-373, E-cadherin and CD44 in laryngeal squamous cell carcinoma and evaluated the association between the disease and clinical characteristics of patients. Tumor tissues were collected from 24 laryngeal cancer patients. Adjacent normal tissue samples were also obtained as controls. After RNA isolation, we assessed the miR-373, E-cadherin and CD44 levels. As endogenous controls, we used the small RNA U6 and GAPDH TaqMan® to normalize the levels of expression of miR-373, E-cadherin and CD44. The fold change in the expression of the genes in larynx tumor and control tissues was calculated using the 2-Î”Î”CT method. miR-373 was significantly upregulated in seventeen tumor samples compared to controls. However, the expression levels of both E-cadherin and CD44 mRNA were found to be significantly downregulated in tumor versus control regions (p=0.026 and p=0.005, respectively). We did not find any significant difference in the expression levels of miR-373, E-cadherin or CD44 and cancer risk factors. miR-373, E-cadherin and CD44 may be involved in the etiopathogenesis of laryngeal cancer. It can be suggested that E-cadherin and CD44 are functional targets of miR-373, but we need further studies to investigate this hypothesis.

Keywords

miRNA Target genes Laryngeal carcinoma.

Timirci-Kahraman, í–zlem, Verim, A., Farooqi, A. A., Turan, S., í–zkan-Küçük, N. E., & Yaylim, ć°lhan. (2017). Expression of miR-373 and its predicted target genes E-cadherin and CD44 in patients with laryngeal squamous cell carcinoma. Cellular and Molecular Biology, 63(12), 29–33. https://doi.org/10.14715/10.14715/cmb/2017.63.12.8

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References

Machiels JP, Lambrecht M, Hanin FX, Duprez T, Gregoire V, Schmitz S, et al. Advances in the management of squamous cell carcinoma of the head and neck. F1000Prime Rep 2014;2:6:44.
Iizuka Y, Yoshimura M, Inokuchi H, Matsuo Y, Nakamura A, Mizowaki T, et al. Recurrence patterns after postoperative radiotherapy for squamous cell carcinoma of the pharynx and larynx. Acta Otolaryngol 2015; 135(1):96-102.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63(1):11-30.
Ye K, Xu JH, Sun YF, Lin JA, Zheng ZG. Characteristics and clinical significance of lymph node metastases near the recurrent laryngeal nerve from thoracic esophageal carcinoma. Genet Mol Res 2014; 13(3):6411-9.
Perez-Ordoñez B, Beauchemin M, Jordan RC. Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 2006; 59(5):445-53.
Yu X, Li Z. The role of microRNAs expression in laryngeal cancer. Oncotarget 2015; 6(27):23297-305.
Li P, Liu H, Wang Z, He F, Wang H, Shi Z, et al. MicroRNAs in laryngeal cancer: implications for diagnosis, prognosis and therapy. Am J Transl Res 2016; 8(5):1935-44.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009 Jan 23;136(2):215-33.
Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 2007; 8(2):93-103.
Babu JM, Prathibha R, Jijith VS, Hariharan R, Pillai MR. A miR-centric view of head and neck cancers. Biochim Biophys Acta 2011; 1816(1):67-72.
Wang Y, Chen M, Tao Z, Hua Q, Chen S, Xiao B. Identification of predictive biomarkers for early diagnosis of larynx carcinoma based on microRNA expression data. Cancer Genet 2013; 206(9-10):340-6.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006; 6(11):857-66.
Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA. MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer 2009; 9(4):293-302.
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.
Usmani A, Shoro AA, Shirazi B, Memon Z. Investigative and extrapolative role of microRNAs' genetic expression in breast carcinoma. Pak J Med Sci 2016; 32(3):766-72.
Enokida H, Yoshino H, Matsushita R, Nakagawa M. The role of microRNAs in bladder cancer. Investig Clin Urol 2016; 1:60-76.
Nakamura K, Sawada K, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer 2016; 15(1):48.
Mizuguchi Y, Takizawa T, Yoshida H, Uchida E. Dysregulated miRNA in progression of hepatocellular carcinoma: A systematic review. Hepatol Res 2016; 46(5):391-406.
Mohammadi A, Mansoori B, Baradaran B. The role of microRNAs in colorectal cancer. Biomed Pharmacother 2016; 84:705-713.
Irani S. miRNAs Signature in Head and Neck Squamous Cell Carcinoma Metastasis: A Literature Review. J Dent (Shiraz) 2016;17(2):71-83.
Wei F, Cao C, Xu X, Wang J. Diverse functions of miR-373 in cancer. J Transl Med 2015; 20;13:162.
Yang K, Handorean AM, Iczkowski KA. MicroRNAs 373 and 520c are downregulated in prostate cancer, suppress CD44 translation and enhance invasion of prostate cancer cells in vitro. Int J Clin Exp Pathol 2009; 2(4):361-9.
Zhang Y, Zhao FJ, Chen LL, Wang LQ, Nephew KP, Wu YL, et al. MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer. Oncotarget 2014; 5(23):12291-303.
Wu W, He X, Kong J, Ye B. Mir-373 affects human lung cancer cells' growth and its E-cadherin expression. Oncol Res 2012; 20(4):163-70
Nakata K, Ohuchida K, Mizumoto K, Aishima S, Oda Y, Nagai E, et al. Micro RNA-373 is down-regulated in pancreatic cancer and inhibits cancer cell invasion. Ann Surg Oncol 2014; 21(4):564-74.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001 Dec;25(4):402-8.
Meng X, Müller V, Milde-Langosch K, Trillsch F, Pantel K, Schwarzenbach H. Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer. Oncotarget 2016; 7(13):16923-35.
Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 2008; 10(2):202-10.
van Roy F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer 2014; 14(2):121-34.
Chen W, Cai F, Zhang B, Barekati Z, Zhong XY. The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol 2013; 34(1):455-62.
Wei F, Cao C, Xu X, Wang J. Diverse functions of miR-373 in cancer. J Transl Med 2015; 20:13:162.
Wang L, Alcon A, Yuan H, Ho J, Li QJ, Martins-Green M. Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells. Integr Biol (Camb) 2011; 3(7):742-54.
Zhang X, Li X, Tan Z, Liu X, Yang C, Ding X, et al. MicroRNA-373 is upregulated and targets TNFAIP1 in human gastric cancer, contributing to tumorigenesis. Oncol Lett 2013; 6(5):1427-1434.
Qiu X, Zhu J, Sun Y, Fan K, Yang DR, Li G, et al. TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR-373-3p expression to alter TGFÎ²R2/p-Smad3 signals. Oncotarget 2015; 6(17):15397-409.

References

Machiels JP, Lambrecht M, Hanin FX, Duprez T, Gregoire V, Schmitz S, et al. Advances in the management of squamous cell carcinoma of the head and neck. F1000Prime Rep 2014;2:6:44.

Iizuka Y, Yoshimura M, Inokuchi H, Matsuo Y, Nakamura A, Mizowaki T, et al. Recurrence patterns after postoperative radiotherapy for squamous cell carcinoma of the pharynx and larynx. Acta Otolaryngol 2015; 135(1):96-102.

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63(1):11-30.

Ye K, Xu JH, Sun YF, Lin JA, Zheng ZG. Characteristics and clinical significance of lymph node metastases near the recurrent laryngeal nerve from thoracic esophageal carcinoma. Genet Mol Res 2014; 13(3):6411-9.

Perez-Ordoñez B, Beauchemin M, Jordan RC. Molecular biology of squamous cell carcinoma of the head and neck. J Clin Pathol 2006; 59(5):445-53.

Yu X, Li Z. The role of microRNAs expression in laryngeal cancer. Oncotarget 2015; 6(27):23297-305.

Li P, Liu H, Wang Z, He F, Wang H, Shi Z, et al. MicroRNAs in laryngeal cancer: implications for diagnosis, prognosis and therapy. Am J Transl Res 2016; 8(5):1935-44.

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009 Jan 23;136(2):215-33.

Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 2007; 8(2):93-103.

Babu JM, Prathibha R, Jijith VS, Hariharan R, Pillai MR. A miR-centric view of head and neck cancers. Biochim Biophys Acta 2011; 1816(1):67-72.

Wang Y, Chen M, Tao Z, Hua Q, Chen S, Xiao B. Identification of predictive biomarkers for early diagnosis of larynx carcinoma based on microRNA expression data. Cancer Genet 2013; 206(9-10):340-6.

Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer 2006; 6(11):857-66.

Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA. MicroRNAs--the micro steering wheel of tumour metastases. Nat Rev Cancer 2009; 9(4):293-302.

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.

Usmani A, Shoro AA, Shirazi B, Memon Z. Investigative and extrapolative role of microRNAs' genetic expression in breast carcinoma. Pak J Med Sci 2016; 32(3):766-72.

Enokida H, Yoshino H, Matsushita R, Nakagawa M. The role of microRNAs in bladder cancer. Investig Clin Urol 2016; 1:60-76.

Nakamura K, Sawada K, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer 2016; 15(1):48.

Mizuguchi Y, Takizawa T, Yoshida H, Uchida E. Dysregulated miRNA in progression of hepatocellular carcinoma: A systematic review. Hepatol Res 2016; 46(5):391-406.

Mohammadi A, Mansoori B, Baradaran B. The role of microRNAs in colorectal cancer. Biomed Pharmacother 2016; 84:705-713.

Irani S. miRNAs Signature in Head and Neck Squamous Cell Carcinoma Metastasis: A Literature Review. J Dent (Shiraz) 2016;17(2):71-83.

Wei F, Cao C, Xu X, Wang J. Diverse functions of miR-373 in cancer. J Transl Med 2015; 20;13:162.

Yang K, Handorean AM, Iczkowski KA. MicroRNAs 373 and 520c are downregulated in prostate cancer, suppress CD44 translation and enhance invasion of prostate cancer cells in vitro. Int J Clin Exp Pathol 2009; 2(4):361-9.

Zhang Y, Zhao FJ, Chen LL, Wang LQ, Nephew KP, Wu YL, et al. MiR-373 targeting of the Rab22a oncogene suppresses tumor invasion and metastasis in ovarian cancer. Oncotarget 2014; 5(23):12291-303.

Wu W, He X, Kong J, Ye B. Mir-373 affects human lung cancer cells' growth and its E-cadherin expression. Oncol Res 2012; 20(4):163-70

Nakata K, Ohuchida K, Mizumoto K, Aishima S, Oda Y, Nagai E, et al. Micro RNA-373 is down-regulated in pancreatic cancer and inhibits cancer cell invasion. Ann Surg Oncol 2014; 21(4):564-74.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001 Dec;25(4):402-8.

Meng X, Müller V, Milde-Langosch K, Trillsch F, Pantel K, Schwarzenbach H. Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer. Oncotarget 2016; 7(13):16923-35.

Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 2008; 10(2):202-10.

van Roy F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer 2014; 14(2):121-34.

Chen W, Cai F, Zhang B, Barekati Z, Zhong XY. The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol 2013; 34(1):455-62.

Wei F, Cao C, Xu X, Wang J. Diverse functions of miR-373 in cancer. J Transl Med 2015; 20:13:162.

Wang L, Alcon A, Yuan H, Ho J, Li QJ, Martins-Green M. Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells. Integr Biol (Camb) 2011; 3(7):742-54.

Zhang X, Li X, Tan Z, Liu X, Yang C, Ding X, et al. MicroRNA-373 is upregulated and targets TNFAIP1 in human gastric cancer, contributing to tumorigenesis. Oncol Lett 2013; 6(5):1427-1434.

Qiu X, Zhu J, Sun Y, Fan K, Yang DR, Li G, et al. TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR-373-3p expression to alter TGFÎ²R2/p-Smad3 signals. Oncotarget 2015; 6(17):15397-409.