PMID- 30470837
OWN - NLM
STAT- MEDLINE
DCOM- 20190520
LR  - 20220420
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 33
IP  - 3
DP  - 2019 Mar
TI  - MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple 
      myeloma cells.
PG  - 739-748
LID - 10.1038/s41375-018-0300-0 [doi]
AB  - Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. 
      T(4;14) MM overexpresses multiple myeloma SET domain-containing protein (MMSET). 
      MMSET has three major isoforms: the full-length form MMSET II and the short 
      isoforms REIIBP and MMSET I. Here we show that the short isoform MMSET I is an 
      oncoprotein that promoted cell survival and tumorigenesis in vitro and in vivo. 
      Gene expression array analysis indicated that MMSET I increased glyoxalase I 
      (GLO1) expression. Chromatin immunoprecipitation (ChIP) coupled with qPCR 
      indicated that MMSET I bound upstream of the GLO1 transcription start site. 
      Ectopic overexpression of MMSET I or its mutants showed MMSET I depended on its C 
      terminus to regulate GLO1 expression. GLO1 knockdown (KD) induced apoptosis and 
      reduced colony formation. MMSET I or GLO1 KD reduced the levels of anti-apoptosis 
      factors such as MCL1 and BCL2. Ectopic overexpression of GLO1 resulted in the 
      significant rescue of KMS11 cells from MMSET I KD-induced apoptosis and 
      glycolysis inhibition. This suggested that GLO1 may be of functional importance 
      target downstream of MMSET I. Cumulatively, our study suggests that MMSET I is an 
      oncoprotein and potential therapeutic target for t(4;14) MM.
FAU - Xie, Zhigang
AU  - Xie Z
AD  - Cancer Science Institute of Singapore, National University of Singapore, 
      Singapore, 117599, Singapore.
FAU - Chooi, Jing Yuan
AU  - Chooi JY
AD  - Department of Medicine, Yong Loo Lin School of Medicine, National University of 
      Singapore, Singapore, 119228, Singapore.
FAU - Toh, Sabrina Hui Min
AU  - Toh SHM
AD  - Cancer Science Institute of Singapore, National University of Singapore, 
      Singapore, 117599, Singapore.
FAU - Yang, Dongxiao
AU  - Yang D
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research 
      (A*STAR), Singapore, 138668, Singapore.
FAU - Basri, Nurhidayah Binte
AU  - Basri NB
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research 
      (A*STAR), Singapore, 138668, Singapore.
FAU - Ho, Ying Swan
AU  - Ho YS
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research 
      (A*STAR), Singapore, 138668, Singapore.
FAU - Chng, Wee Joo
AU  - Chng WJ
AD  - Cancer Science Institute of Singapore, National University of Singapore, 
      Singapore, 117599, Singapore. mdccwj@nus.edu.sg.
AD  - Department of Medicine, Yong Loo Lin School of Medicine, National University of 
      Singapore, Singapore, 119228, Singapore. mdccwj@nus.edu.sg.
AD  - National University Cancer Institute, National University Health System, 
      Singapore, 119228, Singapore. mdccwj@nus.edu.sg.
LA  - eng
GR  - NMRC/OFYIRG/0010/2016/MOH | National Medical Research Council 
      (NMRC)/International
GR  - STaR Investigatorship/MOH | National Medical Research Council 
      (NMRC)/International
GR  - MOE2014-T3-1-006/Ministry of Education - Singapore (MOE)/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181123
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Oncogene Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Repressor Proteins)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (NSD2 protein, human)
RN  - EC 4.4.1.5 (GLO1 protein, human)
RN  - EC 4.4.1.5 (Lactoylglutathione Lyase)
SB  - IM
MH  - Apoptosis/genetics
MH  - Carcinogenesis/genetics
MH  - Cell Line, Tumor
MH  - Cell Survival/genetics
MH  - Chromatin Immunoprecipitation/methods
MH  - Chromosomes, Human, Pair 14/*genetics
MH  - Chromosomes, Human, Pair 4/*genetics
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Glycolysis/genetics
MH  - Histone-Lysine N-Methyltransferase/*genetics
MH  - Humans
MH  - Lactoylglutathione Lyase/*genetics
MH  - Multiple Myeloma/*genetics
MH  - Oncogene Proteins/*genetics
MH  - Protein Isoforms/genetics
MH  - Repressor Proteins/*genetics
MH  - Translocation, Genetic/genetics
EDAT- 2018/11/25 06:00
MHDA- 2019/05/21 06:00
CRDT- 2018/11/25 06:00
PHST- 2017/11/27 00:00 [received]
PHST- 2018/07/05 00:00 [accepted]
PHST- 2018/06/22 00:00 [revised]
PHST- 2018/11/25 06:00 [pubmed]
PHST- 2019/05/21 06:00 [medline]
PHST- 2018/11/25 06:00 [entrez]
AID - 10.1038/s41375-018-0300-0 [pii]
AID - 10.1038/s41375-018-0300-0 [doi]
PST - ppublish
SO  - Leukemia. 2019 Mar;33(3):739-748. doi: 10.1038/s41375-018-0300-0. Epub 2018 Nov 
      23.