Asset Details
Do you wish to reserve the book?
HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications
Do you wish to request the book?
HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
HDAC3 regulates DNMT1 expression in multiple myeloma: therapeutic implications
2017
Overview
Epigenetic signaling pathways are implicated in tumorigenesis and therefore histone deacetylases (HDACs) represent novel therapeutic targets for cancers, including multiple myeloma (MM). Although non-selective HDAC inhibitors show anti-MM activities, unfavorable side effects limit their clinical efficacy. Isoform- and/or class-selective HDAC inhibition offers the possibility to maintain clinical activity while avoiding adverse events attendant to broad non-selective HDAC inhibition. We have previously reported that HDAC3 inhibition, either by genetic knockdown or selective inhibitor BG45, abrogates MM cell proliferation. Here we show that knockdown of
HDAC3
, but not
HDAC1
or
HDAC2
, as well as BG45, downregulate expression of DNA methyltransferase 1 (DNMT1) mediating MM cell proliferation.
DNMT1
expression is regulated by c-Myc, and HDAC3 inhibition triggers degradation of c-Myc protein. Moreover, HDAC3 inhibition results in hyperacetylation of DNMT1, thereby reducing the stability of DNMT1 protein. Combined inhibition of HDAC3 and DNMT1 with BG45 and DNMT1 inhibitor 5-azacytidine (AZA), respectively, triggers synergistic downregulation of DNMT1, growth inhibition and apoptosis in both MM cell lines and patient MM cells. Efficacy of this combination treatment is confirmed in a murine xenograft MM model. Our results therefore provide the rationale for combination treatment using HDAC3 inhibitor with DNMT1 inhibitor to improve patient outcome in MM.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 42/41
/ 45/61
/ 82/80
/ Animals
/ DNA
/ DNA (Cytosine-5-)-Methyltransferase 1 - genetics
/ DNA (Cytosine-5-)-Methyltransferase 1 - metabolism
/ Gene Expression Regulation, Neoplastic - drug effects
/ Histone Deacetylase Inhibitors - pharmacology
/ Histone Deacetylases - metabolism
/ Histones
/ Humans
/ Kinases
/ Medicine
/ Mice
/ Multiple Myeloma - drug therapy
/ Multiple Myeloma - metabolism
/ Multiple Myeloma - pathology
/ Oncology
/ Patients
/ Proteins
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
