Abstract
Objectives
This study aimed to investigate the role of the tRNA aspartic acid methyltransferase 1 (TRDMT1) protein in the development and progression of gastric cancer (GC).
Methods
The 90 GC tissues and 35 paracancerous tissues (gastric mucosa) were collected from patients (31 males and 59 females; average age 66), who were pathologically diagnosed as GC. The expression of TRDMT1 in three GC cell lines (MKN28, BGC823, and MGC803) and tissues from GC patients were detected by western blotting and immunological staining, respectively. The relationship between TRDMT1 expression and clinicopathological parameters in GC patients was explored. TRDMT1 was knocked down by RNAi lentivirus in GC cells. GC cell migration and invasion were analyzed using scratch and transwell assays.
Results
TRDMT1 expression in the GC cell lines was higher than that in the normal gastric mucosal epithelial cell line (P < 0.05). Positive TRDMT1 protein expression in the GC tissue was higher than that in the adjacent tissue. The expression of TRDMT1 was positively associated with tumor size, histological grade, invasion depth, lymph node metastasis, and tumor node metastasis (TNM) stage (P < 0.05). High TRDMT1 expression predicted poor OS of GC patients. Tumor size, differentiation degree, invasion depth, lymph node metastasis, TNM stage, and TRDMT1 expression were independent predictors of the OS of GC patients. Knockdown of TRDMT1 inhibited the migration and invasion of MKN28 cells.
Conclusion
TRDMT1 was highly expressed in GC cell lines and tissues. TRDMT1 expression was independent predictor of the OS of GC patients. TRDMT1 knockdown reduced GC cell migration and invasion. All these results suggested that TRDMT1 has the potential to be used as a target for the diagnosis and treatment of GC.
Similar content being viewed by others
References
Siegel RL, Miller KD, Jemal A (2015) Cancer statistics. CA Cancer J Clin 65:5–29
Chen W, Zheng R, Baade PD et al (2016) Cancer statistics in China. CA Cancer J Clin 66:115–132
Fattahi S, Golpour M, Amjadi-Moheb F et al (2018) DNA methyltransferases and gastric cancer: insight into targeted therapy. Epigenomics 10:1477–1497
Fu D-G (2015) Epigenetic alterations in gastric cancer. Mol Med Rep 12:3223–3230
Fernandez AF, Huidobro C, Fraga MF (2012) De novo DNA methyltransferases: oncogenes, tumor suppressors, or both? Trends Genet 28:474–479
Kim TY, Jong HS, Jung Y et al (2004) DNA hypermethylation in gastric cancer. Aliment Pharmacol Ther 20:131–142
Jin B, Robertson KD (2013) DNA methyltransferases, DNA damage repair, and cancer. Adv Exp Med Biol 754:3
Toyota M, Yamamoto E (2011) DNA methylation changes in cancer. Prog Mol Biol Transl Sci 101:447–457. https://doi.org/10.1016/B978-0-12-387685-0.00014-7
Schaefer M, Lyko F (2010) Solving the Dnmt2 enigma. Chromosoma 119:35–40
Robertson KD (2005) DNA methylation and human disease. Nat Rev Genet 6:597–610
Delaval K, Wagschal A, Feil R (2006) Epigenetic deregulation of imprinting in congenital diseases of aberrant growth. Bioessays 28:453–459
Balada E, Ordi-Ros J, Serrano-Acedo S et al (2008) Transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in CD4+ T cells from patients with systemic lupus erythematosus. Immunology 124:339–347
Yang J, Fang X (2012) Expression of DNMT1, DNMT3a, and DNMT3b in eutopic endometrium. Zhong nan da xue xue bao. Yi xue ban = J Cent South Univ (Med Sci) 37:94–99
Vieira GC, Vieira GF, Sinigaglia M et al (2017) Linking epigenetic function to electrostatics: The DNMT2 structural model example. PloS One. https://doi.org/10.1371/journal.pone.0178643
Li H, Li W, Liu S et al (2016) DNMT1, DNMT3A and DNMT3B polymorphisms associated with gastric cancer risk: a systematic review and meta-analysis. EBioMedicine 13:125–131
Esteller M (2008) Epigenetics in cancer. N Engl J Med 358:1148–1159
Hermann A, Schmitt S, Jeltsch A (2003) The human Dnmt2 has residual DNA-(cytosine-C5) methyltransferase activity. J Biol Chem 278:31717–31721
Goll MG, Kirpekar F, Maggert KA et al (2006) Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311:395–398
El-Deiry WS, Nelkin BD, Celano P et al (1991) High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer. Proc Natl Acad Sci 88:3470–3474
Patra SK, Patra A, Zhao H et al (2002) DNA methyltransferase and demethylase in human prostate cancer. Mol Carcinog 33:163–171
Girault I, Tozlu S, Lidereau R et al (2003) Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Clin Cancer Res 9:4415–4422
Yang X-X, He X-Q, Li F-X et al (2012) Risk-association of DNA methyltransferases polymorphisms with gastric cancer in the Southern Chinese population. Int J Mol Sci 13:8364–8378
Oh B-K, Kim H, Park H-J et al (2007) DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation. Int J Mol Med 20:65–73
Melki J, Warnecke P, Vincent P et al (1998) Increased DNA methyltransferase expression in leukaemia. Leukemia 12:311–316
Kanai Y, Ushijima S, Kondo Y et al (2001) DNA methyltransferase expression and DNA methylation of CPG islands and peri-centromeric satellite regions in human colorectal and stomach cancers. Int J Cancer 91:205–212
Ghanbarian H, Wagner N, Polo B et al (2016) Dnmt2/Trdmt1 as mediator of RNA polymerase II transcriptional activity in cardiac growth. PloS One 11:e0156953. https://doi.org/10.1371/journal.pone.0156953
Xue S, Xu H, Sun Z et al (2019) Depletion of TRDMT1 affects 5-methylcytosine modification of mRNA and inhibits HEK293 cell proliferation and migration. Biochem Biophys Res Commun 520:60–66
Dev RR, Ganji R, Singh SP et al (2017) Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection. Biochem J 474:2009–2026
Lewinska A, Adamczyk-Grochala J, Kwasniewicz E et al (2017) Downregulation of methyltransferase Dnmt2 results in condition-dependent telomere shortening and senescence or apoptosis in mouse fibroblasts. J Cell Physiol 232:3714–3726
Tuorto F, Herbst F, Alerasool N et al (2015) The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J 34:2350–2362
Acknowledgements
None.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Sun, X., Huang, X., Lu, X. et al. The expression and clinical significance of the tRNA aspartic acid methyltransferase 1 protein in gastric cancer. Int J Clin Oncol 26, 2229–2236 (2021). https://doi.org/10.1007/s10147-021-02019-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10147-021-02019-2