Expression CUG-binding Protein 1 and Its Relationship with Prognosis of Non-small Cell Lung Cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

HAOJin-peng ¹ ,  JIAOWen-jie ² , ZHAOYan-dong ² , WANGZi-zong ²

1. Graduate School of Weifang Medical College, Weifang 261053, Shandong, P. R. China;
2. Department of Thoracic Surgery, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong, P. R. China;

Corresponding author：

JIAOWen-jie, Email: xwkjwj@163.com

Keywords：

CUG-binding protein 1; Non-small cell lung cancer; Prognosis

DOI：

10.7507/1007-4848.20140106

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To detect mRNA and protein expression of CUG-binding protein 1(CUGBP1)in non-small cell lung cancer (NSCLC), and assess the prognostic significance of CUGBP1. Methods Fifty-seven NSCLC patients who received surgical resection at the Department of Thoracic Surgery of Affiliated Hospital of Qingdao University between July 2009 and April 2011 were enrolled in this study. There were 32 male and 25 female patients with their age of 43-74 (60.6±8.9) years. The expressions of CUGBP1 mRNA and protein in tumor and adjacent normal tissues were detected by semi-quantitative RT-PCR and immunohistochemistry. All the patients were followed up every 2 months after discharge via the phone. Time to progression(TTP) was used to evaluate the relationship between CUGBP1 mRNA, clinicopathological variables and prognosis. The percentage of CUGBP1 mRNA and CUGBP1 expression was correlated with clinical characteristics using χ² test. The prognostic significance of CUGBP1 mRNA was assessed by univariate and multivariate analysis using Cox regression analysis. Results The expressions of CUGBP1 mRNA and CUGBP1 were over-expressed in cancer tissue, and were significantly correlated with TNM-stage and differentiation. Univariate and multivariate analysis showed that CUGBP1 mRNA expression(P=0.0074, HR=3.701, 95% CI 1.420-9.648), TNM-stage (P < 0.000 1, HR=4.043, 95% CI 2.098-7.794) and age (P=0.0018, HR=3.207, 95% CI 1.544-6.664) were independent predictors of postsurgical survival in NSCLC patients. Conclusions CUGBP1 mRNA and CUGBP1 are over-expressed in NSCLC, and over-expression of CUGBP1 mRNA independently predicts a shorter postsurgical survival in NSCLC patients.

Citation： HAOJin-peng, JIAOWen-jie, ZHAOYan-dong, WANGZi-zong. Expression CUG-binding Protein 1 and Its Relationship with Prognosis of Non-small Cell Lung Cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(3): 389-393. doi: 10.7507/1007-4848.20140106 Copy

1.	Kang S1, Koh ES, Vinod SK, et al. Cost analysis of lung cancer management in South Western Sydney. J Med Imaging Radiat Oncol, 2012, 56 (2):235-241.
2.	Tomita Y, Morioka E, Kaida D, et al. A case of port site recurrence after thoracoscopic resection for lung metastasis of cecal cancer. Gan To Kagaku Ryoho, 2012, 39 (12):1923-1925.
3.	Oji Y, Kitamura Y, Kamino E, et al. WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor. Int J Cancer, 2009, 125 (2):381-387.
4.	Le Tonqueze O, Gschloessl B, Namanda-Vanderbeken A, et al. Chromosome wide analysis of CUGBP1 binding sites identifies the tetraspanin CD9 mRNA as a target for CUGBP1-mediated down-regul ation. Biochem Biophys Res Commun, 2010, 394 (4):884-889.
5.	Timchenko LT, Miller JW, Timchenko NA, et al. Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res, 1996, 24 (22):4407-4414.
6.	Souza D, Lai RY, Shuen M, et al. mRNA stability as a function of striated muscle oxidative capacity. Am J Physiol Regul Integr Comp Physiol, 2012, 303 (4):408-417.
7.	Zhang L, Lee JE, Wilusz J, et al. The RNA-binding protein CUGBP1 regulates stability of tumor necrosis factor mRNA in muscle cells:implications for myotonic dystrophy. J Biol Chem, 2008, 283 (33):22457-22463.
8.	Zheng Y, Miskimins WK. CUG-binding protein represses translation of p27Kip1 mRNA through its internal ribosomal entry site. RNA Biol, 2011, 8 (3):365-371.
9.	Lee JE, Cooper TA. Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans, 2009, 37 (6):1281-1286.
10.	De La Motte Rouge T, Valent A, Ambrosetti D, et al. Clinical and molecular predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Ann Pathol, 2007, 27 (5):353-363.
11.	Benlloch S, Galbis-Caravajal JM, Alenda C, et al. Expression of molecular markers in mediastinal nodes from resected stage I non-small-cell lung cancer (NSCLC):prognostic impact and potential role as markers of occult micrometastases. Ann Oncol, 2009, 20 (1):91-97.
12.	Cui YH, Xiao L, Rao JN, et al. miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies. Mol Biol Cell, 2012, 23 (1):151-162.
13.	Meola G, Jones K, Wei C, et al. Dysfunction of protein homeostasis in myotonic dystrophies. Histol Histopathol, 2013, 28 (9):1089-1098.
14.	Beisang D, Rattenbacher B, Vlasova-St Louis IA, et al. Regulation of CUG-binding protein 1 (CUGBP1)binding to target transcripts upon T cell activation. J Biol Chem, 2012, 287 (2):950-960.
15.	Xiao L, Cui YH, Rao JN, et al. Regulation of cyclin-dependent kinase 4 translation through CUG-binding protein 1 and microRNA-222 by polyamines. Mol Biol Cell, 2011, 22(17):3055-3069.
16.	Huichalaf C, Sakai K, Jin B, et al. Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1)cells. FASEB J, 2010, 24 (10):3706-3719.
17.	Salisbury E, Sakai K, Schoser B, et al. Ectopic expression of cyclin D3 corrects differentiation of DM1 myoblasts through activation of RNA CUG-binding protein, CUGBP1. Exp Cell Res, 2008, 314 (11-12):2266-2278.
18.	Arnal-Estape A, Tarragona M, Morales M, et al. HER2 silences tumor suppression in breast cancer cells by switching expression of C/EBPss isoforms. Cancer Res, 2010, 70 (23):9927-9936.
19.	Rattenbacher B, Beisang D, Wiesner DL, et al. Analysis of CUGBP1 targets identifies GU-repeat sequences that mediate rapid mRNA decay. Mol Cell Biol, 2010, 30 (16):3970-3980.
20.	代学利, 申屠阳. Ⅰb期非小细胞肺癌患者手术预后因素分析.中国胸心血管外科临床杂志, 2009, 16 (5):353-356.

1. Kang S1, Koh ES, Vinod SK, et al. Cost analysis of lung cancer management in South Western Sydney. J Med Imaging Radiat Oncol, 2012, 56 (2):235-241.
2. Tomita Y, Morioka E, Kaida D, et al. A case of port site recurrence after thoracoscopic resection for lung metastasis of cecal cancer. Gan To Kagaku Ryoho, 2012, 39 (12):1923-1925.
3. Oji Y, Kitamura Y, Kamino E, et al. WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor. Int J Cancer, 2009, 125 (2):381-387.
4. Le Tonqueze O, Gschloessl B, Namanda-Vanderbeken A, et al. Chromosome wide analysis of CUGBP1 binding sites identifies the tetraspanin CD9 mRNA as a target for CUGBP1-mediated down-regul ation. Biochem Biophys Res Commun, 2010, 394 (4):884-889.
5. Timchenko LT, Miller JW, Timchenko NA, et al. Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucleic Acids Res, 1996, 24 (22):4407-4414.
6. Souza D, Lai RY, Shuen M, et al. mRNA stability as a function of striated muscle oxidative capacity. Am J Physiol Regul Integr Comp Physiol, 2012, 303 (4):408-417.
7. Zhang L, Lee JE, Wilusz J, et al. The RNA-binding protein CUGBP1 regulates stability of tumor necrosis factor mRNA in muscle cells:implications for myotonic dystrophy. J Biol Chem, 2008, 283 (33):22457-22463.
8. Zheng Y, Miskimins WK. CUG-binding protein represses translation of p27Kip1 mRNA through its internal ribosomal entry site. RNA Biol, 2011, 8 (3):365-371.
9. Lee JE, Cooper TA. Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans, 2009, 37 (6):1281-1286.
10. De La Motte Rouge T, Valent A, Ambrosetti D, et al. Clinical and molecular predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer. Ann Pathol, 2007, 27 (5):353-363.
11. Benlloch S, Galbis-Caravajal JM, Alenda C, et al. Expression of molecular markers in mediastinal nodes from resected stage I non-small-cell lung cancer (NSCLC):prognostic impact and potential role as markers of occult micrometastases. Ann Oncol, 2009, 20 (1):91-97.
12. Cui YH, Xiao L, Rao JN, et al. miR-503 represses CUG-binding protein 1 translation by recruiting CUGBP1 mRNA to processing bodies. Mol Biol Cell, 2012, 23 (1):151-162.
13. Meola G, Jones K, Wei C, et al. Dysfunction of protein homeostasis in myotonic dystrophies. Histol Histopathol, 2013, 28 (9):1089-1098.
14. Beisang D, Rattenbacher B, Vlasova-St Louis IA, et al. Regulation of CUG-binding protein 1 (CUGBP1)binding to target transcripts upon T cell activation. J Biol Chem, 2012, 287 (2):950-960.
15. Xiao L, Cui YH, Rao JN, et al. Regulation of cyclin-dependent kinase 4 translation through CUG-binding protein 1 and microRNA-222 by polyamines. Mol Biol Cell, 2011, 22(17):3055-3069.
16. Huichalaf C, Sakai K, Jin B, et al. Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1)cells. FASEB J, 2010, 24 (10):3706-3719.
17. Salisbury E, Sakai K, Schoser B, et al. Ectopic expression of cyclin D3 corrects differentiation of DM1 myoblasts through activation of RNA CUG-binding protein, CUGBP1. Exp Cell Res, 2008, 314 (11-12):2266-2278.
18. Arnal-Estape A, Tarragona M, Morales M, et al. HER2 silences tumor suppression in breast cancer cells by switching expression of C/EBPss isoforms. Cancer Res, 2010, 70 (23):9927-9936.
19. Rattenbacher B, Beisang D, Wiesner DL, et al. Analysis of CUGBP1 targets identifies GU-repeat sequences that mediate rapid mRNA decay. Mol Cell Biol, 2010, 30 (16):3970-3980.
20. 代学利, 申屠阳. Ⅰb期非小细胞肺癌患者手术预后因素分析.中国胸心血管外科临床杂志, 2009, 16 (5):353-356.

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Expression CUG-binding Protein 1 and Its Relationship with Prognosis of Non-small Cell Lung Cancer

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