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当代肿瘤药物靶点

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

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Research Article

镁依赖性磷酸酶（MDP）1是胃癌的潜在抑制剂。

卷 19, 期 10, 2019

页: [817 - 827] 页: 11

弟呕挨: 10.2174/1568009619666190620112546

价格: $65

摘要

背景：复发是胃癌（GC）患者治疗失败和死亡的主要原因。但是，GC复发的潜在机制仍不清楚，并且仍缺乏预后指标。 方法：我们分析了生存期较短（<1年）或生存期较长（> 3年）的胃癌患者的DNA甲基化谱，并鉴定了与GC复发相关的候选基因。然后，研究了这些基因对胃癌的生物学作用。 结果：一个新的基因，镁依赖性磷酸酶1（mdp1），被鉴定为候选基因，该基因的DNA甲基化在较短生存期患者的GC样品中较高，而在较长生存期患者中较低。 MDP1蛋白在GC组织中高表达，具有更长的生存时间，并且也倾向于在高分化GC样品中表达。 MDP1在GC细胞系BGC-823中的强迫表达抑制细胞增殖，而敲低MDP1蛋白则促进细胞生长。 MDP1在BGC-823细胞中的过表达也增强了细胞的衰老和凋亡。发现胞质激酶蛋白c-Jun N-末端激酶（JNK）和信号转导和转录激活因子3（Stat3）介导MDP1的生物学功能。 结论：这些结果表明MDP1蛋白抑制胃癌细胞的存活，而MDP表达的丧失可能有利于胃癌的复发。

关键词: 胃癌，预后标志物，镁依赖性磷酸酶1，DNA甲基化，MDP1蛋白，细胞质激酶蛋白。

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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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