PMID- 28415746
OWN - NLM
STAT- MEDLINE
DCOM- 20180319
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 23
DP  - 2017 Jun 6
TI  - Epigenetic up-regulation of ribosome biogenesis and more aggressive phenotype 
      triggered by the lack of the histone demethylase JHDM1B in mammary epithelial 
      cells.
PG  - 37091-37103
LID - 10.18632/oncotarget.16181 [doi]
AB  - The alterations of ribosome biogenesis and protein synthesis play a direct role 
      in the development of tumors. The accessibility and transcription of ribosomal 
      genes is controlled at several levels, with their epigenetic regulation being one 
      of the most important. Here we explored the JmjC domain-containing histone 
      demethylase 1B (JHDM1B) function in the epigenetic control of rDNA transcription. 
      Since JHDM1B is a negative regulator of gene transcription, we focused on the 
      effects induced by JHDM1B knock-down (KD). We studied the consequences of stable 
      inducible JHDM1B silencing in cell lines derived from transformed and 
      untransformed mammary epithelial cells. In these cellular models, prolonged 
      JHDM1B downregulation triggered a surge of 45S pre-rRNA transcription and 
      processing, associated with a re-modulation of the H3K36me2 levels at rDNA loci 
      and with changes in DNA methylation of specific CpG sites in rDNA genes. We also 
      found that after JHDM1B KD, cells showed a higher ribosome content: which were 
      engaged in mRNA translation. JHDM1B KD and the consequent stimulation of 
      ribosomes biogenesis conferred more aggressive features to the tested cellular 
      models, which acquired a greater clonogenic, staminal and invasive potential. 
      Taken together, these data indicate that the reduction of JHDM1B leads to a more 
      aggressive cellular phenotype in mammary gland cells, by virtue of its negative 
      regulatory activity on ribosome biogenesis.
FAU - Galbiati, Alice
AU  - Galbiati A
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Penzo, Marianna
AU  - Penzo M
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Bacalini, Maria Giulia
AU  - Bacalini MG
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Onofrillo, Carmine
AU  - Onofrillo C
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Guerrieri, Ania Naila
AU  - Guerrieri AN
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Garagnani, Paolo
AU  - Garagnani P
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Franceschi, Claudio
AU  - Franceschi C
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Trere, Davide
AU  - Trere D
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
FAU - Montanaro, Lorenzo
AU  - Montanaro L
AD  - Department of Experimental, Diagnostic, and Specialty Medicine, Alma Mater 
      Studiorum, University of Bologna, Bologna, Italy.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (F-Box Proteins)
RN  - 0 (Histones)
RN  - 0 (RNA, Ribosomal)
RN  - 0 (RNA, ribosomal, 45S)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.14.11.27 (KDM2A protein, human)
SB  - IM
MH  - Animals
MH  - Breast/cytology
MH  - Breast Neoplasms/genetics/pathology/therapy
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - *Epigenesis, Genetic
MH  - Epithelial Cells/*metabolism
MH  - F-Box Proteins/*genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Histones/metabolism
MH  - Humans
MH  - Jumonji Domain-Containing Histone Demethylases/*genetics/metabolism
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Phenotype
MH  - RNA Interference
MH  - RNA, Ribosomal/genetics/metabolism
MH  - RNAi Therapeutics/methods
MH  - Ribosomes/*genetics/metabolism
MH  - *Up-Regulation
MH  - Xenograft Model Antitumor Assays/methods
PMC - PMC5514893
OTO - NOTNLM
OT  - JHDM1B
OT  - cancer cells
OT  - histone modification
OT  - rDNA
OT  - ribosome biogenesis
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2017/04/19 06:00
MHDA- 2018/03/20 06:00
PMCR- 2017/06/06
CRDT- 2017/04/19 06:00
PHST- 2016/04/28 00:00 [received]
PHST- 2017/03/03 00:00 [accepted]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2018/03/20 06:00 [medline]
PHST- 2017/04/19 06:00 [entrez]
PHST- 2017/06/06 00:00 [pmc-release]
AID - 16181 [pii]
AID - 10.18632/oncotarget.16181 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jun 6;8(23):37091-37103. doi: 10.18632/oncotarget.16181.