%0 Journal Article %1 murraystewart2016epigenetic %A Murray-Stewart, Tracy %A Sierra, Johanna C %A Piazuelo, M. Blanca %A Mera, Robertino M %A Chaturvedi, Rupesh %A Bravo, Luis E %A Correa, Pelayo %A Schneider, Barbara G %A Wilson, Keith T %A Casero, Robert A, Jr %D 2016 %J Oncogene %K 7 cancer epigenetics methylation mirnas pathogens %N 42 %P 5480-5488 %R 10.1038/onc.2016.91 %T Epigenetic silencing of miR-124 prevents spermine oxidase regulation: Implications for Helicobacter pylori-induced gastric cancer %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050049/ %V 35 %X Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2 production by >50% within 24 hours. Reporter assays indicated that direct interaction of miR-124 with the 3′-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 prior to infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer.

@article{murraystewart2016epigenetic, abstract = {Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2 production by >50% within 24 hours. Reporter assays indicated that direct interaction of miR-124 with the 3′-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 prior to infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer.}, added-at = {2017-10-19T15:21:20.000+0200}, author = {Murray-Stewart, Tracy and Sierra, Johanna C and Piazuelo, M. Blanca and Mera, Robertino M and Chaturvedi, Rupesh and Bravo, Luis E and Correa, Pelayo and Schneider, Barbara G and Wilson, Keith T and {Casero, Robert A}, Jr}, biburl = {https://www.bibsonomy.org/bibtex/210b66516ce76975b45776feff4f6ac80/artheibault}, description = {Infection by Helicobacter pylori increases risk of gastric cancer through upregulation of the SMOX pathway. This article focuses on methylation of miR-124, a regulator of SMOX, in H. pylori infected cells and its implications for gastric cancer risk. It is the sixth recent article, the seventh article in total, that I have selected to analyze, and provides yet another piece in the puzzle of how H. pylori contributes to gastric cancer.}, doi = {10.1038/onc.2016.91}, interhash = {81e90d049b9aeb6654f23b6214101004}, intrahash = {10b66516ce76975b45776feff4f6ac80}, journal = {Oncogene}, keywords = {7 cancer epigenetics methylation mirnas pathogens}, month = oct, number = 42, pages = {5480-5488}, timestamp = {2017-10-25T21:47:58.000+0200}, title = {Epigenetic silencing of miR-124 prevents spermine oxidase regulation: Implications for Helicobacter pylori-induced gastric cancer}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5050049/}, volume = 35, year = 2016 }