BMC Gastroenterology | |
Up-regulation of CNDP2 facilitates the proliferation of colon cancer | |
Hanping Shi3  Mingyong Miao2  Ting Yang1  Kaitao Yuan3  Miao Yu3  Honglan Yu3  Zhenwei Zhang2  Conglong Xue3  | |
[1] Department of Intensive Care Unit, Zhongshan people’s Hospital, 2 Sunwen East Road, Zhongshan, Guangdong 528403, China;Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China;Department of Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, Guangdong 510080, China | |
关键词: RNA interference; Clinicopathological Characteristics; Poliferation; Colon cancer; CNDP2; | |
Others : 855210 DOI : 10.1186/1471-230X-14-96 |
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received in 2013-07-24, accepted in 2014-05-14, 发布年份 2014 | |
【 摘 要 】
Background
Cytosolic nonspecific dipetidase (CN2) belongs to the family of M20 metallopeptidases. It was stated in previous articles that higher expression levels of CN2 were observed in renal cell carcinoma and breast cancer. Our study explored the correlation between CN2 and colon carcinogenesis.
Methods
We analysed the relationship between 183 patients clinicopathological characteristics and its CN2 expression. To detect the levels of CN2 in colon cancer cell lines and colon cancer tissues by western blot. To verify cell proliferation in colon cancer cells with knockdown of CNDP2 and explore the causes of these phenomena.
Results
The expression levels of CN2 in clinical colon tumors and colon cancer cell lines were significantly higher than that in normal colon mucosa and colon cell lines. The difference in CN2 levels was associated with tumor location (right- and left-sided colon cancer), but there was no significant association with age, gender, tumor size, tumor grade, tumor stage or serum carcinoembryonic antigen (CEA). Knockdown of CNDP2 inhibited cell proliferation, blocked cell cycle progression and retarded carcinogenesis in an animal model. The signaling pathway through which knockdown of CNDP2 inhibited cell proliferation and tumorigenesis involved in EGFR, cyclin B1 and cyclin E.
Conclusions
Knockdown of CNDP2 can inhibit the proliferation of colon cancer in vitro and retarded carcinogenesis in vivo.
【 授权许可】
2014 Xue et al.; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
- [2]Bufill JA: Colorectal cancer: evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med 1990, 113:779-788.
- [3]Hutchins G, Southward K, Handley K, Magill L, Beaumont C, Stahlschmidt J, Richman S, Chambers P, Seymour M, Kerr D, Gray R, Quirke P: Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011, 29:1261-1270.
- [4]Teufel M, Saudek V, Ledig JP, Bernhardt A, Boularand S, Carreau A, Cairns NJ, Carter C, Cowley DJ, Duverger D, Ganzhorn AJ, Guenet C, Heintzelmann B, Laucher V, Sauvage C, Smirnova T: Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase. J Biol Chem 2003, 278:6521-6531.
- [5]Pandya V, Ekka MK, Dutta RK, Kumaran S: Mass spectrometry assay for studying kinetic properties of dipeptidases: characterization of human and yeast dipeptidases. Anal Biochem 2011, 418:134-142.
- [6]Renner C, Zemitzsch N, Fuchs B, Geiger KD, Hermes M, Hengstler J, Gebhardt R, Meixensberger J, Gaunitz F: Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model. Mol Cancer 2010, 9:2. BioMed Central Full Text
- [7]Iovine B, Iannella ML, Nocella F, Pricolo MR, Bevilacqua MA: Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS production. Cancer Lett 2012, 315:122-128.
- [8]Ichinose Y, Genka K, Koike T, Kato H, Watanabe Y, Mori T, Iioka S, Sakuma A, Ohta M: NK421 Lung Cancer Surgery Group. Randomized double-blind placebo-controlled trial of bestatin in patients with resected stage I squamous-cell lung carcinoma. J Natl Cancer Inst 2003, 95:605-610.
- [9]Tripathi A, King C, de la Morenas A, Perry VK, Burke B, Antoine GA, Hirsch EF, Kavanah M, Mendez J, Stone M, Gerry NP, Lenburg ME, Rosenberg CL: Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients. Int J Cancer 2008, 122:1557-1566.
- [10]Okamura N, Masuda T, Gotoh A, Shirakawa T, Terao S, Kaneko N, Suganuma K, Watanabe M, Matsubara T, Seto R, Matsumoto J, Kawakami M, Yamamori M, Nakamura T, Yagami T, Sakaeda T, Fujisawa M, Nishimura O, Okumura K: Quantitative proteomic analysis to discover potential diagnostic markers and therapeutic targets in human renal cell carcinoma. Proteomics 2008, 8:3194-3203.
- [11]Perroud B, Ishimaru T, Borowsky AD, Weiss RH: Grade-dependent proteomics characterization of kidney cancer. Mol Cell Proteomics 2009, 8:971-985.
- [12]Lee JH, Giovannetti E, Hwang JH, Petrini I, Wang Q, Voortman J, Wang Y, Steinberg SM, Funel N, Meltzer PS, Wang Y, Giaccone G: Loss of 18q22.3 involving the carboxypeptidase of glutamate-like gene is associated with poor prognosis in resected pancreatic cancer. Clin Cancer Res 2012, 18:524-533.
- [13]Zhang P, Chan DW, Zhu Y, Li JJ, Ng IO, Wan D, Gu J: Identification of carboxypeptidase of glutamate like-B as a candidate suppressor in cell growth and metastasis in human hepatocellular carcinoma. Clin Cancer Res 2006, 12:6617-6625.
- [14]Boldyrev AA, Aldini G, Derave W: Physiology and pathophysiology of carnosine. Physiol Rev 2013, 93:1803-1845.
- [15]Lindblom A: Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Curr Opin Oncol 2001, 13:63-69.
- [16]Nawa T, Kato J, Kawamoto H, Okada H, Yamamoto H, Kohno H, Endo H, Shiratori Y: Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology. J Gastroenterol Hepatol 2008, 23:418-423.
- [17]Benedix F, Kube R, Meyer F, Schmidt U, Gastinger I, Lippert H: Colon/Rectum Carcinomas (Primary Tumor) Study Group. Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum 2010, 53:57-64.
- [18]Knoblich JA, Sauer K, Jones L, Richardson H, Saint R, Lehner CF: Cyclin E controls S phase progression and its down-regulation during Drosophila embryogenesis is required for the arrest of cell proliferation. Cell 1994, 77:107-120.
- [19]Aleem E, Kiyokawa H, Kaldis P: Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat Cell Biol 2005, 7:831-836.
- [20]Kitahara K, Yasui W, Kuniyasu H, Yokozaki H, Akama Y, Yunotani S, Hisatsugu T, Tahara E: Concurrent amplification of cyclin E and CDK2 genes in colorectal carcinomas. Int J Cancer 1995, 62:25-28.
- [21]Pinto AE, André S, Pereira T, Nóbrega S, Soares J: Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma. J Clin Pathol 2001, 54:543-549.
- [22]Pinto AE, Silva GL, Pereira T, Cabrera RA, Santos JR, Leite V: S-phase fraction and ploidy as predictive markers in primary disease and recurrence of papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2012, 77:302-309.
- [23]Khanna R, Agarwal A, Khanna S, Basu S, Khanna AK: S-phase fraction and DNA ploidy in oral leukoplakia. ANZ J Surg 2010, 80:548-551.
- [24]Salud A, Porcel JM, Raikundalia B, Camplejohn RS, Taub NA: Prognostic significance of DNA ploidy, S-phase fraction, and P-glycoprotein expression in colorectal cancer. J Surg Oncol 1999, 72:167-174.
- [25]Bazan V, Migliavacca M, Zanna I, Tubiolo C, Corsale S, Calò V, Amato A, Cammareri P, Latteri F, Grassi N, Fulfaro F, Porcasi R, Morello V, Nuara RB, Dardanoni G, Salerno S, Valerio MR, Dusonchet L, Gerbino A, Gebbia N, Tomasino RM, Russo A: DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study. J Cancer Res Clin Oncol 2002, 128:650-658.
- [26]Mollah ML, Park DK, Park HJ: Cordyceps militaris Grown on Germinated Soybean Induces G2/M Cell Cycle Arrest through Downregulation of Cyclin B1 and Cdc25c in Human Colon Cancer HT-29 Cells. Evid Based Complement Alternat Med 2012, 2012:249217.
- [27]Archer SY, Johnson J, Kim HJ, Ma Q, Mou H, Daesety V, Meng S, Hodin RA: The histone deacetylase inhibitor butyrate downregulates cyclin B1 gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells. Am J Physiol Gastrointest Liver Physiol 2005, 289:696-703.
- [28]Baker NE, Yu SY: The EGF receptor defines domains of cell cycle progression and survival to regulate cell number in the developing Drosophila eye. Cell 2001, 104:699-708.
- [29]Lim YC, Cha YY: Epigallocatechin-3-gallate induces growth inhibition and apoptosis of human anaplastic thyroid carcinoma cells through suppression of EGFR/ERK pathway and cyclin B1/CDK1 complex. J Surg Oncol 2011, 104:776-780.