Journals / Turkish Journal of Medical Sciences / 2019 / Cilt: 49 - Sayı: 5

Nicotinamide N-methyltransferase expression and its association with phospho-Akt, p53 expression, and survival in high-grade endometrial cancer

Pages
1547–1554
Publication Date
2022-11-05
DOI
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

NNMT’s role in cancer progression could make it a target of EC therapy.

📌 3 Key Takeaways

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Objective & Hypothesis:Background/aim: Nicotinamide N-methyltransferase (NNMT) is an enzyme that is overexpressed in malignancies.
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Key Findings & Data:Increased phospho-Akt (pAkt) levels in response to NNMT overexpressionhave been reported in in vitro studies of different cancer types.
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Conclusion & Impact:NNMT’s role in cancer progression could make it a target of EC therapy.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Background/aim: Nicotinamide N-methyltransferase (NNMT) is an enzyme that is overexpressed in malignancies. NNMT expressionhas not been previously studied in endometrial cancer (EC). Increased phospho-Akt (pAkt) levels in response to NNMT overexpressionhave been reported in in vitro studies of different cancer types. We assayed NNMT expression in primary and metastatic high-grade ECand investigated the relationship of NNMT with p53, pAkt, and survival.Materials and methods: NNMT, pAkt, and p53 expressions were assayed in 100 tissue samples of benign endometria, primary EC, andmetastatic EC by immunohistochemistry.Results: The NNMT immunoreactivity score was significantly higher in primary high-grade EC than benign endometrial tissue (P =0.001). NNMT expression in metastatic tissue was significantly higher than in primary cancer (P < 0.001). Metastatic stromal NNMTexpression was significantly higher than that of the adjacent tumor and stroma adjacent to the primary tumor. p53 expression inthe primary tumor showed a significant positive correlation with omental NNMT and pAkt expression. NNMT expression was alsocorrelated with pAkt expression in metastatic tissue. NNMT overexpression in metastatic tissue was associated with decreased survival(P = 0.039).Conclusion: This study suggests that NNMT may promote cancer progression and that NNMT overexpression is associated withaberrant p53 expression, pAkt, and poor survival. NNMT’s role in cancer progression could make it a target of EC therapy.

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Cite This Article

UĞRAŞ, S., ÇELİK, Ç., HARMANKAYA, İ., AKAR, S. (2022). Nicotinamide N-methyltransferase expression and its association with phospho-Akt, p53 expression, and survival in high-grade endometrial cancer. Turkish Journal of Medical Sciences, Cilt: 49 - Sayı: 5, 1547–1554. https://ajindex.com/articles/609971

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References (12)

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer Journal for Clinicians 2016
  2. doi: 10.3322/ caac.21551 2. Felix AS, Weissfeld JL, Stone RA, Bowser R, Chivukula M et al. Factors associated with type I and type II endometrial cancer. Cancer Causes & Control 2010
  3. doi: 10.1007/ s10552-010-9612-8 3. Moore KN, Fader AN. Uterine papillary serous carcinoma. Clinical Obstetrics and Gynecology 2011
  4. doi: 10.1097/GRF.0b013e318218c755 4. Sartini D, Seta R, Pozzi V, Morganti S, Rubini C et al. Role of nicotinamide N-methyltransferase in non-small cell lung cancer: in vitro effect of shRNA-mediated gene silencing on tumourigenicity. Biological Chemistry 2015
  5. 396 (3): 225-234. doi: 10.1515/hsz-2014-0231 5. Palanichamy K, Kanji S, Gordon N, Thirumoorthy K, Jacob JR et al. NNMT silencing activates tumor suppressor PP2A, inactivates oncogenic STKs, and inhibits tumor forming ability. Clinical Cancer Research 2017
  6. 23 (9): 2325-2334. doi: 10.1158/1078-0432.CCR-16-1323 6. Chen C, Wang X, Huang X, Yong H, Shen J et al. Nicotinamide N-methyltransferase: a potential biomarker for worse prognosis in gastric carcinoma. American Journal of Cancer Research 2016
  7. 6 (3): 649-663. 7. Xu Y, Liu P, Zheng DH, Wu N, Zhu L et al. Expression profile and prognostic value of NNMT in patients with pancreatic cancer. Oncotarget 2016
  8. 7 (15): 19975-19981. doi: 10.18632/ oncotarget.7891 8. Xie X, Liu H, Wang Y, Zhou Y, Yu H et al. Nicotinamide N-methyltransferase enhances resistance to 5-fluorouracil in colorectal cancer cells through inhibition of the ASK1-p38 MAPK pathway. Oncotarget 2016
  9. 7 (29): 45837-45848. doi: 10.18632/oncotarget.9962 9. Ulanovskaya OA, Zuhl AM, Cravatt BF. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nature Chemical Biology 2013
  10. 9 (5): 300- 306. doi: 10.1038/nchembio.1204 10. Kanska J, Aspuria PP, Taylor-Harding B, Spurka L, Funari V et al. Glucose deprivation elicits phenotypic plasticity via ZEB1-mediated expression of NNMT. Oncotarget 2017
  11. 8 (16): 26200-26220. doi: 10.18632/oncotarget.15429 11. Eckert MA, Coscia F, Chryplewicz A, Chang JW, Hernandez KM et al. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature 2019
  12. 569 (7758): 723-728. doi: 10.1038/s41586-019-1173-8 12. Bach DH, Kim D, Bae SY, Kim WK, Hong JY et al. Targeting nicotinamide N-methyltransferase and miR-449a in EGFRTKI-resistant non-small-cell lung cancer cells.