Nicotinamide N-methyltransferase is overexpressed in prostate cancer and correlates with prolonged progression-free and overall survival times

Zhou, Weimin; Gui, Ming; Zhu, Min; Li, Zhi; Huang, Lihua; Zhou, Jun; He, Leye; Zhong, Kuangbiao

doi:10.3892/ol.2014.2287

Cited by 32 publications

(31 citation statements)

References 27 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In prostate carcinoma, enzyme levels were negatively correlated with Gleason score. Contrary to what above reported for other neoplasms, NNMT expression was significantly associated with prolonged progression‐free survival and overall survival in patients diagnosed with advanced prostate cancer . Results obtained from a recent study, carried out in a cohort of patients with gastric cancer, revealed that NNMT tumour expression is positively related to primary tumour size, lymph node or distant metastasis and pathological stage.…”

Section: Discussioncontrasting

confidence: 70%

“…Contrary to what above reported for other neoplasms, NNMT expression was significantly associated with prolonged progression-free survival and overall survival in patients diagnosed with advanced prostate cancer. 37 Results obtained from a recent study, carried out in a cohort of patients with gastric cancer, revealed that NNMT tumour expression is positively related to primary tumour size, lymph node or distant metastasis and pathological stage. Kaplan-Meier curves demonstrated that NNMT represents an important negative prognostic predictor of overall survival of gastric cancer patients.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Pompei

Salvolini

Rubini

et al. 2019

Eur J Clin Investigation

View full text Add to dashboard Cite

Background Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the most common forms of nonmelanoma skin cancers (NMSCs). Although successful treatment of these neoplasms is based on surgical excision, an increasing number of BCCs relapses and many SCCs display high rates of recurrence and metastasis. Nicotinamide N‐methyltransferase (NNMT) is a cytosolic enzyme, which was found to be upregulated in different solid tumours. However, there are no data regarding enzyme expression in NMSCs. The aim of this study was therefore to evaluate the potential involvement of NNMT in BCCs and SCCs. Materials and methods Immunohistochemical analyses were carried out on 40 BCC cases and 39 SCC cases, to evaluate enzyme expression in tumour and surrounding healthy margins. Moreover, the relationship between NNMT intratumour levels and clinico‐pathological parameters were explored. Results Nicotinamide N‐methyltransferase was found to be overexpressed in BCCs compared with control tissues, while a significant enzyme downregulation was detected in SCCs with respect to corresponding healthy margins. In addition, NNMT levels were negatively related to aggressiveness of both BCCs (distinguishing between infiltrative and nodular tumours) and SCCs (considering head and neck forms and tumours of the extremities and trunk). Conclusions These evidences seem to demonstrate that the different NNMT dysregulation detected in BCC and SCC may be the result of important biological traits distinctively characterizing these two forms within NMSCs. In addition, enzyme levels seem to be inversely correlated with tumour aggressiveness, thus suggesting the potential suitability of the enzyme as a prognostic biomarker for both neoplasms.

show abstract

Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 98%

Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Pompei

Salvolini

Rubini

et al. 2019

Eur J Clin Investigation

View full text Add to dashboard Cite

show abstract

“…NNMT is a cytosolic enzyme that catalyzes the N-methylation of NCA, pyridines and analogues using S-adenosyl-L-methionine (AdoMet) as the methyl donor. Previous studies have examined the effects of NNMT knockdown or overexpression on various cancer cell phenotypes in vitro , yielding conflicting results49505152. Some of them identified positive correlation between overexpression of NNMT and tumor cell aggressiveness5051.…”

Section: Discussionmentioning

confidence: 99%

Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior

Mobley

Zhang

Bondaruk

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA’s effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.

show abstract

“…NNMT expression was not correlated with increasing fat mass in HFD mice, but is elevated when mice consume HFD. Research on NNMT has largely focused on its association with carcinogenesis [28,29]. Likewise SIRT7 has also been implicated in carcinogenesis [30,31].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding

Drew

Farquharson

Horgan

et al. 2016

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

The sirtuin (SIRT)/nicotinamide adenine dinucleotide (NAD) system is implicated in development of type 2 diabetes (T2D) and diet-induced obesity, a major risk factor for T2D. Mechanistic links have not yet been defined. SIRT/NAD system gene expression and NAD/NADH levels were measured in liver, white adipose tissue (WAT) and skeletal muscle from mice fed either a low-fat diet or high-fat diet (HFD) for 3 days up to 16 weeks. An in-house custom-designed multiplex gene expression assay assessed all 7 mouse SIRTs (SIRT1-7) and 16 enzymes involved in conversion of tryptophan, niacin, nicotinamide riboside and metabolic precursors to NAD. Significantly altered transcription was correlated with body weight, fat mass, plasma lipids and hormones. Regulation of the SIRT/NAD system was associated with early (SIRT4, SIRT7, NAPRT1 and NMNAT2) and late phases (NMNAT3, NMRK2, ABCA1 and CD38) of glucose intolerance. TDO2 and NNMT were identified as markers of HFD consumption. Altered regulation of the SIRT/NAD system in response to HFD was prominent in liver compared with WAT or muscle. Multiple components of the SIRTs and NAD biosynthetic enzymes network respond to consumption of dietary fat. Novel molecular targets identified above could direct strategies for dietary/therapeutic interventions to limit metabolic dysfunction and development of T2D.

show abstract

Nicotinamide N-methyltransferase is overexpressed in prostate cancer and correlates with prolonged progression-free and overall survival times

Cited by 32 publications

References 27 publications

Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior

Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding

Contact Info

Product

Resources

About