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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

Magnesium-dependent Phosphatase (MDP) 1 is a Potential Suppressor of Gastric Cancer

Author(s): Jianbo Zhu, Lijuan Deng, Baozhen Chen, Wenqing Huang, Xiandong Lin, Gang Chen, Chi-Meng Tzeng*, Mingang Ying* and Zhongxian Lu*

Volume 19, Issue 10, 2019

Page: [817 - 827] Pages: 11

DOI: 10.2174/1568009619666190620112546

Price: $65

Abstract

Background: Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.

Methods: We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.

Results: A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.

Conclusion: These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.

Keywords: Gastric cancer, prognosis marker, magnesium-dependent phosphatase 1, DNA methylation, MDP1 protein, Cytoplasmic kinase protein.

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[1]
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61(2), 69-90.
[http://dx.doi.org/10.3322/caac.20107] [PMID: 21296855]
[2]
Harada, K.; Mizrak Kaya, D.; Shimodaira, Y.; Ajani, J.A. Global chemotherapy development for gastric cancer. Gastric Cancer, 2017, 20(Suppl. 1), 92-101.
[http://dx.doi.org/10.1007/s10120-016-0655-8] [PMID: 27718136]
[3]
Lochhead, P.; El-Omar, E.M. Molecular Predictors of Gastric Neoplastic Progression. Cancer Cell, 2018, 33(1), 9-11.
[http://dx.doi.org/10.1016/j.ccell.2017.12.006] [PMID: 29316435]
[4]
Xie, Y.; Zhou, J.J.; Zhao, Y.; Zhang, T.; Mei, L.Z.H.H. pylori modifies methylation of global genomic DNA and the gastrin gene promoter in gastric mucosal cells and gastric cancer cells. Microb. Pathog., 2017, 108, 129-136.
[http://dx.doi.org/10.1016/j.micpath.2017.05.003] [PMID: 28478202]
[5]
Gigek, C.O.; Calcagno, D.Q.; Rasmussen, L.T.; Santos, L.C.; Leal, M.F.; Wisnieski, F.; Burbano, R.R.; Lourenço, L.G.; Lopes-Filho, G.J.; Smith, M.A.C. Genetic variants in gastric cancer: Risks and clinical implications. Exp. Mol. Pathol., 2017, 103(1), 101-111.
[http://dx.doi.org/10.1016/j.yexmp.2017.07.004] [PMID: 28736214]
[6]
Hartgrink, H.H.; Jansen, E.P.; van Grieken, N.C.; van de Velde, C.J. Gastric cancer. Lancet, 2009, 374(9688), 477-490.
[http://dx.doi.org/10.1016/S0140-6736(09)60617-6] [PMID: 19625077]
[7]
Guo, J.; Yu, W.; Su, H.; Pang, X. Genomic landscape of gastric cancer: Molecular classification and potential targets. Sci. China Life Sci., 2017, 60(2), 126-137.
[http://dx.doi.org/10.1007/s11427-016-0034-1] [PMID: 27460193]
[8]
Shiraishi, N.; Inomata, M.; Osawa, N.; Yasuda, K.; Adachi, Y.; Kitano, S. Early and late recurrence after gastrectomy for gastric carcinoma. Univariate and multivariate analyses. Cancer, 2000, 89(2), 255-261.
[http://dx.doi.org/10.1002/1097-0142(20000715)89:2<255:AID-CNCR8>3.0.CO;2-N] [PMID: 10918153]
[9]
Böhner, H.; Zimmer, T.; Hopfenmüller, W.; Berger, G.; Buhr, H.J. Detection and prognosis of recurrent gastric cancer-is routine follow-up after gastrectomy worthwhile? Hepatogastroenterology, 2000, 47(35), 1489-1494.
[PMID: 11100384]
[10]
Abbas, M.; Habib, M.; Naveed, M.; Karthik, K.; Dhama, K.; Shi, M.; Dingding, C. The relevance of gastric cancer biomarkers in prognosis and pre- and post- chemotherapy in clinical practice. Biomed. Pharmacother., 2017, 95, 1082-1090.
[http://dx.doi.org/10.1016/j.biopha.2017.09.032] [PMID: 28922727]
[11]
Nakamura, J.; Tanaka, T.; Kitajima, Y.; Noshiro, H.; Miyazaki, K. Methylation-mediated gene silencing as biomarkers of gastric cancer: a review. World J. Gastroenterol., 2014, 20(34), 11991-12006.
[http://dx.doi.org/10.3748/wjg.v20.i34.11991] [PMID: 25232236]
[12]
Ushijima, T.; Asada, K. Aberrant DNA methylation in contrast with mutations. Cancer Sci., 2010, 101(2), 300-305.
[http://dx.doi.org/10.1111/j.1349-7006.2009.01434.x] [PMID: 19958364]
[13]
Laird, P.W. The power and the promise of DNA methylation markers. Nat. Rev. Cancer, 2003, 3(4), 253-266.
[http://dx.doi.org/10.1038/nrc1045] [PMID: 12671664]
[14]
Choi, S.J.; Jung, S.W.; Huh, S.; Chung, Y.S.; Cho, H.; Kang, H. Alteration of DNA Methylation in Gastric Cancer with Chemotherapy. J. Microbiol. Biotechnol., 2017, 27(8), 1367-1378.
[PMID: 28621113]
[15]
Oh, J.H.; Jung, S.H.; Hong, S.J.; Rhyu, M.G. DNA Methylation as Surrogate Marker For Gastric Cancer. J. Cancer Prev., 2015, 20(3), 172-178.
[http://dx.doi.org/10.15430/JCP.2015.20.3.172] [PMID: 26473155]
[16]
Shimizu, D.; Kanda, M.; Kodera, Y. Review of recent molecular landscape knowledge of gastric cancer. Histol. Histopathol., 2018, 33(1), 11-26.
[PMID: 28447336]
[17]
Panarese, I.; De Vita, F.; Ronchi, A.; Romano, M.; Alfano, R.; Di Martino, N.; Zito Marino, F.; Ferraraccio, F.; Franco, R. Predictive biomarkers along gastric cancer pathogenetic pathways. Expert Rev. Anticancer Ther., 2017, 17(5), 417-425.
[http://dx.doi.org/10.1080/14737140.2017.1301207] [PMID: 28277834]
[18]
Selengut, J.D. MDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases. Biochemistry, 2001, 40(42), 12704-12711.
[http://dx.doi.org/10.1021/bi011405e] [PMID: 11601995]
[19]
Ezra Peisach, J.D.S. Dunaway-Mariano, Debra; Allen, Karen N. X-ray Crystal Structure of the Hypothetical Phosphotyrosine Phosphatase MDP-1 ofthe Haloacid Dehalogenase Superfamily. biochemistry, 2004, 43(40), 12770-12779.
[20]
Seifried, A.; Schultz, J.; Gohla, A. Human HAD phosphatases: structure, mechanism, and roles in health and disease. The FEBS Journal, 2013, 280(2), 549-571.
[21]
Cheng, J.; Zhong, Y.; Chen, S.; Sun, Y.; Huang, L.; Kang, Y.; Chen, B.; Chen, G.; Wang, F.; Tian, Y.; Liu, W.; Feng, G.S.; Lu, Z. Gab2 mediates hepatocellular carcinogenesis by integrating multiple signaling pathways. FASEB J., 2017, 31(12), 5530-5542.
[http://dx.doi.org/10.1096/fj.201700120RR] [PMID: 28842424]
[22]
Nie, Y.; Wu, K.; Yu, J.; Liang, Q.; Cai, X.; Shang, Y.; Zhou, J.; Pan, K.; Sun, L.; Fang, J.; Yuan, Y.; You, W.; Fan, D. A global burden of gastric cancer: the major impact of China. Expert Rev. Gastroenterol. Hepatol., 2017, 11(7), 651-661.
[http://dx.doi.org/10.1080/17474124.2017.1312342] [PMID: 28351219]
[23]
Obermannová, R.; Lordick, F. Management of metastatic gastric cancer. Hematol. Oncol. Clin. North Am., 2017, 31(3), 469-483.
[http://dx.doi.org/10.1016/j.hoc.2017.01.006] [PMID: 28501088]
[24]
Maeda, M.; Moro, H.; Ushijima, T. Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: Aberrant DNA methylation pathway. Gastric Cancer, 2017, 20(Suppl. 1), 8-15.
[http://dx.doi.org/10.1007/s10120-016-0650-0] [PMID: 27718135]
[25]
Yamashita, M.; Toyota, M.; Suzuki, H.; Nojima, M.; Yamamoto, E.; Kamimae, S.; Watanabe, Y.; Kai, M.; Akashi, H.; Maruyama, R.; Sasaki, Y.; Yamano, H.; Sugai, T.; Shinomura, Y.; Imai, K.; Tokino, T.; Itoh, F. DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae. Cancer Sci., 2010, 101(7), 1708-1716.
[http://dx.doi.org/10.1111/j.1349-7006.2010.01581.x] [PMID: 20507321]
[26]
Qiu, Y.S.; Liao, G.J.; Jiang, N.N. DNA Methylation-Mediated Silencing of regenerating protein 1 Alpha (REG1A) affects gastric cancer prognosis. Med. Sci. Monit., 2017, 23, 5834-5843.
[http://dx.doi.org/10.12659/MSM.904706] [PMID: 29222406]
[27]
Alonzo, T.A.; Siegmund, K.D. Statistical methods for evaluating DNA methylation as a marker for early detection or prognosis. Dis. Markers, 2007, 23(1-2), 113-120.
[http://dx.doi.org/10.1155/2007/308573] [PMID: 17325431]
[28]
Ikoma, H.; Ichikawa, D.; Koike, H.; Ikoma, D.; Tani, N.; Okamoto, K.; Ochiai, T.; Ueda, Y.; Otsuji, E.; Yamagishi, H. Correlation between serum DNA methylation and prognosis in gastric cancer patients. Anticancer Res., 2006, 26(3B), 2313-2316.
[PMID: 16821608]
[29]
Raja, U.M.; Gopal, G.; Rajkumar, T. Intragenic DNA methylation concomitant with repression of ATP4B and ATP4A gene expression in gastric cancer is a potential serum biomarker. Asian Pac. J. Cancer Prev., 2012, 13(11), 5563-5568.
[http://dx.doi.org/10.7314/APJCP.2012.13.11.5563] [PMID: 23317218]
[30]
Choi, B.; Han, T.S.; Min, J.; Hur, K.; Lee, S.M.; Lee, H.J.; Kim, Y.J.; Yang, H.K. MAL and TMEM220 are novel DNA methylation markers in human gastric cancer. Biomarkers, 2017, 22(1), 35-44.
[http://dx.doi.org/10.1080/1354750X.2016.1201542] [PMID: 27329150]
[31]
Tahara, T.; Tahara, S.; Horiguchi, N.; Kawamura, T.; Okubo, M.; Yamada, H.; Yoshida, D.; Ohmori, T.; Maeda, K.; Komura, N.; Ikuno, H.; Jodai, Y.; Kamano, T.; Nagasaka, M.; Nakagawa, Y.; Tsukamoto, T.; Urano, M.; Shibata, T.; Kuroda, M.; Ohmiya, N. Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients. Clin. Exp. Med., 2018, 18(2), 215-220.
[http://dx.doi.org/10.1007/s10238-017-0471-4] [PMID: 28871451]
[32]
Chen, Y.; Lin, J.; Yang, M.; Xu, C.W.; Chen, B.Z.; Li, X.J.; Zhu, W.F.; Fu, W.D.; Yu, H.; Ying, M.G.; Chen, G. Expression and prognostic roles of magnesium-dependent phosphatase-1 in gastric cancer. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(11), 2617-2625.
[PMID: 28678323]

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