Roles of MTH1 gene in the occurrence and treatment of cancers

doi:10.3760/cma.j.issn.1673-422X.2016.01.007

Abstract

Abstract: MTH1 protein can mitigate DNA damage which caused by reactive oxygen species through hydrolyzing oxidized deoxyribonucleoside triphosphate. MTH1 is highly expressed in various cancers, so as to maintain the viability of cancer cells. MTH1 is closely related to tumor associated genes such as microRNA, RAS gene and p53 gene. Moreover, MTH1 inhibitors can selectively suppress the proliferation of cancers, which is a potential new target in tumor therapy.

Key words: Neoplasms, Reactive oxygen species, Targeted therapy

Guan Xuwen, Huang Dingzhi. Roles of MTH1 gene in the occurrence and treatment of cancers[J]. Journal of International Oncology, 2016, 43(1): 26-28.

References

［1］ Patel A, Burton DG, Halvorsen K, et al. MutT Homolog 1 (MTH1) maintains multiple KRASdriven promalignant pathways［J］. Oncogene, 2015, 34(20): 2586-2596. DOI:10.1038/onc.2014.195. ［2］ Speina E, Arczewska KD, Gackowski D, et al. Contribution of hMTH1 to the maintenance of 8oxoguanine levels in lung DNA of nonsmallcell lung cancer patients［J］. J Natl Cancer Inst, 2005, 97(5): 384-395. ［3］ Borrego S, Vazquez A, Dasí F, et al. Oxidative stress and DNA damage in human gastric carcinoma: 8Oxo7′8dihydro2′deoxyguanosine (8oxodG) as a possible tumor marker［J］. Int J Mol Sci, 2013, 14(2): 3467-3486. DOI:10.3390/ijms14023467. ［4］ Gad H, Koolmeister T, Jemth AS, et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool［J］. Nature, 2014, 508(7495): 215-221. DOI:10.1038/nature13181. ［5］ Kim HS, Jung G. Notch1 increases snail expression under high reactive oxygen species conditions in hepatocellular carcinoma cells［J］. Free Radic Res, 2014, 48(7): 806-813. DOI:10.3109/10715762.2014.909595. ［6］ Qu Y, Dang S, Hou P. Gene methylation in gastric cancer ［J］. Clin Chim Acta［J］, 2013, 424: 53-65. DOI: 10.1016/j.cca.2013.05.002. ［7］ Weinberg F, Hamanaka R, Wheaton WW, et al. Mitochondrial metabolism and ROS generation are essential for Krasmediated tumorigenicity［J］. Proc Natl Acad Sci USA, 2010, 107(19): 8788-8793. DOI:10.1073/pnas.1003428107. ［8］ Song WJ, Jiang P, Cai JP, et al. Expression of cytoplasmic 8oxoGsn and MTH1 correlates with pathological grading in human gastric cancer［J］. Asian Pac J Cancer Prev, 2015, 16(15): 6335-6338. DOI:10.7314/APJCP.2015.16.15.6335. ［9］ Tsuzuki T, Egashira A, Igarashi H, et al. Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8oxodGTPase［J］. Proc Natl Acad Sci USA, 2001, 98(20): 11456-11461. ［10］ Ohno M, Sakumi K, Fukumura R, et al. 8oxoguanine causes spontaneous de novo germline mutations in mice［J］. Sci Rep, 2014, 4: 4689. DOI:10.1038/srep04689. ［11］ Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis［J］. Science, 2011, 331(6024): 15591564. DOI:10.1126/science.1203543. ［12］ Qi L, Sun B, Liu Z, et al. Wnt3a expression is associated with epithelialmesenchymal transition and promotes colon cancer progression［J］. J Exp Clin Cancer Res, 2014, 33: 107. DOI:10.1186/s13046-014-0107-4. ［13］ Rai P. Human Mut T Homolog 1 (MTH1): a roadblock for the tumorsuppressive effects of oncogenic RASinduced ROS［J］. Small GTPases, 2012, 3(2): 120-125. DOI:10.4161/sgtp.19556. ［14］ Rai P, Young JJ, Burton DG, et al. Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RASinduced DNA damage and premature senescence［J］. Oncogene, 2010, 30(12): 14891496. DOI:10.1038/onc.2010.520. ［15］ Yan X, Chen X, Liang H, et al. miR143 and miR145 synergistically regulate ERBB3 to suppress cell proliferation and invasion in breast cancer ［J］. Mol Cancer, 2014, 13: 220. DOI: 10.1186/1476-4598-13-220. ［16］ Cho WC, Chow AS, Au JS. MiR145 inhibits cell proliferation of human lung adenocarcinoma by targeting EGFR and NUDT1［J］. RNA Biol, 2011, 8(1): 125-131. ［17］ Huber KV, Salah E, Radic B, et al. Stereospecific targeting of MTH1 by (S)crizotinib as an anticancer strategy［J］. Nature, 2014, 508(7495): 222-227. DOI:10.1038/nature13194. ［18］ Streib M, Krling K, Richter K, et al. An organometallic inhibitor for the human repair enzyme 7,8dihydro8oxoguanosine triphosphatase［J］. Angew Chem Int Ed Engl, 2014, 53(1): 305309. DOI:10.1002/anie.201307849. ［19］ Smits VA, Gillespie DA. Cancer therapy. Targeting the poison within［J］. Cell Cycle, 2014, 13(15): 2330-2333. ［20］ Gao W, Cao W, Sun Y, et al. AuNP flarescapped mesoporous silica nanoplatform for MTH1 detection and inhibition［J］. Biomaterials, 2015, 69: 212-221. DOI:10.1016/j.biomaterials.2015.08.021. ［21］ Zhu Y, Zhang L, Zhang GD, et al. Potential mechanisms of benzyl isothiocyanate suppression of invasion and angiogenesis by the U87MG human glioma cell line［J］. Asian Pac J Cancer Prev, 2014, 15(19): 8225-8228. ［22］ Helleday T. Cancer phenotypic lethality, exemplified by the nonessential MTH1 enzyme being required for cancer survival［J］. Ann Oncol, 2014, 25(7): 1253-1255. DOI:10.1093/annonc/mdu158.

[1]	Liu Na, Kou Jieli, Yang Feng, Liu Taotao, Li Danping, Han Junrui, Yang Lizhou. Clinical value of serum miR-106b-5p and miR-760 combined with low-dose spiral CT in the diagnosis of early lung cancer [J]. Journal of International Oncology, 2024, 51(6): 321-325.
[2]	Yang Mi, Bie Jun, Zhang Jiayong, Deng Jiaxiu, Tang Zuge, Lu Jun. Analysis of the efficacy and prognosis of neoadjuvant therapy for locally advanced resectable esophageal cancer [J]. Journal of International Oncology, 2024, 51(6): 332-337.
[3]	Yuan Jian, Huang Yanhua. Diagnostic value of Hp-IgG antibody combined with serum DKK1 and sB7-H3 in early gastric cancer [J]. Journal of International Oncology, 2024, 51(6): 338-343.
[4]	Chen Hongjian, Zhang Suqing. Study on the relationship between serum miR-24-3p， H2AFX and clinical pathological features and postoperative recurrence in liver cancer patients [J]. Journal of International Oncology, 2024, 51(6): 344-349.
[5]	Guo Zehao, Zhang Junwang. Role of PFDN and its subunits in tumorigenesis and tumor development [J]. Journal of International Oncology, 2024, 51(6): 350-353.
[6]	Zhang Baihong, Yue Hongyun. Advances in anti-tumor drugs with new mechanisms of action [J]. Journal of International Oncology, 2024, 51(6): 354-358.
[7]	Xu Fenglin, Wu Gang. Research progress of EBV in tumor immune microenvironment and immunotherapy of nasopharyngeal carcinoma [J]. Journal of International Oncology, 2024, 51(6): 359-363.
[8]	Wang Ying, Liu Nan, Guo Bing. Advances of antibody-drug conjugate in the therapy of metastatic breast cancer [J]. Journal of International Oncology, 2024, 51(6): 364-369.
[9]	Zhang Rui, Chu Yanliu. Research progress of colorectal cancer risk assessment models based on FIT and gut microbiota [J]. Journal of International Oncology, 2024, 51(6): 370-375.
[10]	Gao Fan, Wang Ping, Du Chao, Chu Yanliu. Research progress on intestinal flora and non-surgical treatment of the colorectal cancer [J]. Journal of International Oncology, 2024, 51(6): 376-381.
[11]	Liu Jing, Liu Qin, Huang Mei. Prognostic model construction of lung infection in patients with chemoradiotherapy for esophageal cancer based on SMOTE algorithm [J]. Journal of International Oncology, 2024, 51(5): 267-273.
[12]	Yang Lin, Lu Ning, Wen Hua, Zhang Mingxin, Zhu Lin. Study on the clinical relationship between inflammatory burden index and gastric cancer [J]. Journal of International Oncology, 2024, 51(5): 274-279.
[13]	Wang Junyi, Hong Kaibin, Ji Rongjia, Chen Dachao. Effect of cancer nodules on liver metastases after radical resection of colorectal cancer [J]. Journal of International Oncology, 2024, 51(5): 280-285.
[14]	Zhang Ningning, Yang Zhe, Tan Limei, Li Zhenning, Wang Di, Wei Yongzhi. Diagnostic value of cervical cell DNA ploidy analysis combined with B7-H4 and PKCδ for cervical cancer [J]. Journal of International Oncology, 2024, 51(5): 286-291.
[15]	Fu Yi, Ma Chenying, Zhang Lu, Zhou Juying. Research progress of habitat analysis in radiomics of malignant tumors [J]. Journal of International Oncology, 2024, 51(5): 292-297.