N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis

Hui Chang Bi, Yu Zhuo Pan, Jing Xin Qiu, Kristopher W. Krausz, Fei Li, Caroline H.Johnson, Chang Tao Jiang, Frank J. Gonzalez, Aiming Yu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography- mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding micro- RNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis.

Original languageEnglish (US)
Pages (from-to)2264-2272
Number of pages9
JournalCarcinogenesis
Volume35
Issue number10
DOIs
StatePublished - 2014

Fingerprint

Nicotinamide N-Methyltransferase
Metabolome
MicroRNAs
Carcinogenesis
Carnitine
Heterografts
Untranslated RNA
Messenger RNA
Metabolomics
Niacinamide
Epigenomics
Liquid Chromatography
Mass Spectrometry
Neoplasms
Fatty Acids
Cell Proliferation
Pancreatic Carcinoma
N-methylnicotinamide
Neoplasm Metastasis

ASJC Scopus subject areas

  • Medicine(all)
  • Cancer Research

Cite this

N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. / Bi, Hui Chang; Pan, Yu Zhuo; Qiu, Jing Xin; Krausz, Kristopher W.; Li, Fei; H.Johnson, Caroline; Jiang, Chang Tao; Gonzalez, Frank J.; Yu, Aiming.

In: Carcinogenesis, Vol. 35, No. 10, 2014, p. 2264-2272.

Research output: Contribution to journalArticle

Bi, Hui Chang ; Pan, Yu Zhuo ; Qiu, Jing Xin ; Krausz, Kristopher W. ; Li, Fei ; H.Johnson, Caroline ; Jiang, Chang Tao ; Gonzalez, Frank J. ; Yu, Aiming. / N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. In: Carcinogenesis. 2014 ; Vol. 35, No. 10. pp. 2264-2272.
@article{ce28f4362a9941d4acd2618d49d5932a,
title = "N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis",
abstract = "The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography- mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding micro- RNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis.",
author = "Bi, {Hui Chang} and Pan, {Yu Zhuo} and Qiu, {Jing Xin} and Krausz, {Kristopher W.} and Fei Li and Caroline H.Johnson and Jiang, {Chang Tao} and Gonzalez, {Frank J.} and Aiming Yu",
year = "2014",
doi = "10.1093/carcin/bgu174",
language = "English (US)",
volume = "35",
pages = "2264--2272",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis

AU - Bi, Hui Chang

AU - Pan, Yu Zhuo

AU - Qiu, Jing Xin

AU - Krausz, Kristopher W.

AU - Li, Fei

AU - H.Johnson, Caroline

AU - Jiang, Chang Tao

AU - Gonzalez, Frank J.

AU - Yu, Aiming

PY - 2014

Y1 - 2014

N2 - The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography- mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding micro- RNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis.

AB - The cell metabolome comprises abundant information that may be predictive of cell functions in response to epigenetic or genetic changes at different stages of cell proliferation and metastasis. An unbiased ultra-performance liquid chromatography- mass spectrometry-based metabolomics study revealed a significantly altered metabolome for human pancreatic carcinoma PANC-1 cells with gain-of-function non-coding micro- RNA-1291 (miR-1291), which led to a lower migration and invasion capacity as well as suppressed tumorigenesis in a xenograft tumor mouse model. A number of metabolites, including N-methylnicotinamide, involved in nicotinamide metabolism, and l-carnitine, isobutyryl-carnitine and isovaleryl-carnitine, involved in fatty acid metabolism, were elevated in miR-1291-expressing PANC-1. Notably, N-methylnicotinamide was elevated to the greatest extent, and this was associated with a sharp increase in nicotinamide N-methyltransferase (NNMT) mRNA level in miR-1291-expressing PANC-1 cells. In addition, expression of NNMT mRNA was inversely correlated with pancreatic tumor size in the xenograft mouse model. These results indicate that miR-1291-altered PANC-1 cell function is associated with the increase in N-methylnicotinamide level and NNMT expression, and in turn NNMT may be indicative of the extent of pancreatic carcinogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84964316047&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964316047&partnerID=8YFLogxK

U2 - 10.1093/carcin/bgu174

DO - 10.1093/carcin/bgu174

M3 - Article

C2 - 25115443

AN - SCOPUS:84964316047

VL - 35

SP - 2264

EP - 2272

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 10

ER -