Functional mechanism of malate dehydrogenase 2 in tumors

doi:10.3760/cma.j.issn.1673-422X.2019.03.010

Abstract

Abstract: The role of malate dehydrogenase 2 (MDH2) in tumors is doublesided, it has a cancerpromoting effect in some tumors and an inhibitory effect in other tumors. The function of MDH2 is related to energy metabolism, tumor resistance and its pseudo hypoxia. MDH2 plays an important role in the occurrence, development, invasion and metastasis of tumors. An indepth understanding of the functional mechanism of MDH2 in tumors can provide new molecular targets for tumor intervention in the clinic.

Key words: Oxidoreductases, Neoplasms, Malate dehydrogenase 2

Wu Ying1, Fu Baixue, Dai Lu, Huang Jun, Teng Yibin, Li Linlin, Zhang Jingwen, Huang Yuhong. Functional mechanism of malate dehydrogenase 2 in tumors[J]. Journal of International Oncology, 2019, 46(3): 178-180.

References

［1］ Liu R, Wang H, Liu J, et al. Uncovering the embryonic developmentrelated proteome and metabolome signatures in breast muscle and intramuscular fat of fastand slowgrowing chickens［J］. BMC Genomics, 2017, 18(1): 816. DOI: 10.1186/s1286401741503. ［2］ AitElMkadem S, DayemQuere M, Gusic M, et al. Mutations in MDH2, encoding a Krebs cycle enzyme, cause earlyonset severe encephalopathy［J］. Am J Hum Genet, 2017, 100(1): 151159. DOI: 10.1016/j.ajhg.2016.11.014. ［3］ Oldham WM, Clish CB, Yang Y, et al. Hypoxiamediated increases in L2hydroxyglutarate coordinate the metabolic response to reductive stress［J］. Cell Metab, 2015, 22(2): 291303. DOI: 10.1016/j.cmet.2015.06.021. ［4］ Lo YW, Lin ST, Chang SJ, et al. Mitochondrial proteomics with siRNA knockdown to reveal ACAT1 and MDH2 in the development of doxorubicinresistant uterine cancer［J］. J Cell Mol Med, 2015, 19(4): 744759. DOI: 10.1111/jcmm.12388. ［5］ Kim BS, Lee K, Jung HJ, et al. HIF1α suppressing small molecule, LW6, inhibits cancer cell growth by binding to calcineurin b homologous protein 1［J］. Biochem Biophys Res Commun, 2015, 458(1): 1420. DOI: 10.1016/j.bbrc.2015.01.031. ［6］ Taniguchi S, Shimatani Y, Fujimori M, et al. Tumortargeting therapy using geneengineered anaerobicnonpathogenic bifidobacterium longum［J］. Methods Mol Biol, 2016, 1409: 4960. DOI: 10.1007/9781493935154_5. ［7］ Zhuang Y, Xiang J, Bao W, et al. MDH2 stimulated by estrogenGPR30 pathway downregulated PTEN expression promoting the proliferation and invasion of cells in endometrial cancer［J］. Transl Oncol, 2017, 10(2): 203210. DOI: 10.1016/j.tranon.2017.01.009. ［8］ Ban HS, Xu X, Jang K, et al. A novel malate dehydrogenase 2 inhibitor suppresses hypoxiainducible factor1 by regulating mitochondrial respiration［J］. PLoS One, 2016, 11(9): e0162568. DOI: 10.1371/journal.pone.0162568. ［9］ Wei J, Yang Y, Lu M, et al. Recent advances in the discovery of HIF1αp300/CBP inhibitors as anticancer agents［J］. Mini Rev Med Chem, 2018, 18(4): 296309. DOI: 10.2174/1389557516666160630124938. ［10］ Lima Queiroz A, Zhang B, Comstock DE, et al. miR1265p targets malate dehydrogenase 1 in nonsmall cell lung carcinomas［J］. Biochem Biophys Res Commun, 2018, 499(2): 314320. DOI: 10.1016/j.bbrc.2018.03.154. ［11］ Latonen L, Afyouniab E, Jylh A, et al. Integrative proteomics in prostate cancer uncovers robustness against genomic and transcriptomic aberrations during disease progression［J］. Nat Commun, 2018, 9(1): 1176. DOI: 10.1038/s41467018035736. ［12］ Cascón A, CominoMéndez I, CurrásFreixes M, et al. Wholeexome sequencing identifies MDH2 as a new familial paragangliomagene［J］. J Natl Cancer Inst, 2015, 107(5): pii: djv053. DOI: 10.1093/jnci/djv053. ［13］ Liu Y, Asnani A, Zou L, et al. Visnagin protects against doxorubicininduced cardiomyopathy through modulation of mitochondrial malate dehydrogenase［J］. Sci Transl Med, 2014, 6(266): 266170. DOI: 10.1126/scitranslmed.3010189. ［14］ Beezhold K, Byersdorfer CA. Targeting immunometabolism to improve anticancer therapies［J］. Cancer Lett, 2018, 414: 127135. DOI: 10.1016/j.canlet.2017.11.005. ［15］ Ylip A, Kivinummi K, Kohvakka A, et al. Transcriptome sequencing reveals PCAT5 as a novel ERGregulated long noncoding RNA in prostate cancer［J］. Cancer Res, 2015, 75(19): 40264031. DOI: 10.1158/00085472.CAN150217. ［16］ Kratochvilova M, Raudenska M, Heger Z, et al. Amino acid profiling of zinc resistant prostate cancer cell lines: associations with cancer progression［J］. Prostate, 2017, 77(6): 604616. DOI: 10.1002/pros.23304. ［17］ Shen H, Hau E, Joshi S, et al. Sensitization of glioblastoma cells to irradiation by modulating the glucose metabolism［J］. Mol Cancer Ther, 2015, 14(8): 17941804. DOI: 10.1158/15357163.MCT150247. ［18］ Gentric G, Kieffer Y, Mieulet V, et al. PMLregulated mitochondrial metabolism enhances chemosensitivity in human ovarian cancers［J］. Cell Metab, 2019, 29(1): 156173.e10. DOI: 10.1016/j.cmet.2018.09.002. ［19］ Zhang B, Tornmalm J, Widengren J, et al. Characterization of the role of the malate dehydrogenases to lung tumor cell survival［J］. J Cancer, 2017, 8(11): 20882096. DOI: 10.7150/jca.19373. ［20］ Xi L. Visnagin—a new protectant against doxorubicin cardiotoxicity? Inhibition of mitochondrial malate dehydrogenase 2 (MDH2) and beyond［J］. Ann Transl Med, 2016, 4(4): 65. DOI: 10.3978/j.issn.23055839.2015.10.43. ［21］ Ippolito L, Marini A, Cavallini L, et al. Metabolic shift toward oxidative phosphorylation in docetaxel resistant prostate cancer cells［J］. Oncotarget, 2016, 7(38): 6189061904. DOI: 10.18632/oncotarget.11301. ［22］ Ciccarone F, Vegliante R, Di Leo L, et al. The TCA cycle as a bridge between oncometabolism and DNA transactions in cancer［J］. Semin Cancer Biol, 2017, 47: 5056. DOI: 10.1016/j.semcancer.2017.06.008. ［23］ Jochmanová I, Zhuang Z, Pacak K. Pheochromocytoma: gasping for air［J］. Horm Cancer, 2015, 6(56): 191205. DOI: 10.1007/s1267201502314. ［24］ Chen C, Zhang LG, Liu J, et al. Bioinformatics analysis of differentially expressed proteins in prostate cancer based on proteomics data［J］. Onco Targets Ther, 2016, 9: 15451557. DOI: 10.2147/OTT.S98807.

[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.