PMID- 28182012
OWN - NLM
STAT- MEDLINE
DCOM- 20171031
LR  - 20230120
IS  - 2041-4889 (Electronic)
VI  - 8
IP  - 2
DP  - 2017 Feb 9
TI  - Loss of BRG1 induces CRC cell senescence by regulating p53/p21 pathway.
PG  - e2607
LID - 10.1038/cddis.2017.1 [doi]
AB  - Brahma-related gene-1 (BRG1) is the specific ATPase of switch/sucrose 
      nonfermentable chromatin-remodeling complex that is aberrantly expressed or 
      mutated in various cancers. However, the exact role of BRG1 in oncogenesis 
      remains unknown. In this study, we demonstrate that the knockdown (KD) of BRG1 
      promotes cellular senescence by influencing the SIRT1/p53/p21 signal axis in 
      colorectal cancer (CRC). In particular, we reveal that the expression level of 
      BRG1 is inversely correlated with p21, one of the classic senescence regulators, 
      and is decreased in senescent CRC cells. KD of BRG1 promoting senescence is 
      indicated by the increase of senescence-associated beta-galactosidase (SA-beta-gal) 
      activity, inhibition of cell proliferation, induction of cell cycle arrest, and 
      formation of senescence-associated heterochromatin foci. BRG1 binds to SIRT1 and 
      interferes with SIRT1-mediated deacetylation of p53 at K382. Rescue experiments 
      by co-silencing p53 or treatment with EX527, a SIRT1-specific inhibitor, 
      abrogated the cellular senescence induced by KD of BRG1. BRG1 KD cells resulted 
      in smaller tumor formation than that in control cells in vivo. Collectively, our 
      study shows that BRG1 has an important role in cellular senescence and tumor 
      growth. The BRG1/SIRT1/p53 signal axis is a novel mechanism of cell senescence in 
      CRC and is a new potential target for cancer therapy.
FAU - Wang, Guihua
AU  - Wang G
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Fu, Yinjia
AU  - Fu Y
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Hu, Fuqing
AU  - Hu F
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Lan, Jinqing
AU  - Lan J
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Xu, Feng
AU  - Xu F
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Yang, Xi
AU  - Yang X
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Luo, Xuelai
AU  - Luo X
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Immunology, Tongji Medical College, Huazhong University of Science 
      and Technology, Wuhan, China.
FAU - Hu, Junbo
AU  - Hu J
AD  - Cancer Research Institute, Tongji Hospital, Huazhong University of Science and 
      Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170209
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Heterochromatin)
RN  - 0 (Nuclear Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 3.6.1.- (SMARCA4 protein, human)
RN  - EC 3.6.4.- (DNA Helicases)
SB  - IM
EIN - Cell Death Dis. 2021 Oct 1;12(10):895. PMID: 34599151
MH  - Animals
MH  - Cell Cycle Checkpoints/physiology
MH  - Cell Proliferation/physiology
MH  - Cell Transformation, Neoplastic/metabolism
MH  - Cellular Senescence/*physiology
MH  - Colorectal Neoplasms/*metabolism/pathology
MH  - Cyclin-Dependent Kinase Inhibitor p21/*metabolism
MH  - DNA Helicases/*metabolism
MH  - Female
MH  - HCT116 Cells
MH  - HT29 Cells
MH  - Heterochromatin/metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Nuclear Proteins/*metabolism
MH  - Signal Transduction/*physiology
MH  - Sirtuin 1/metabolism
MH  - Transcription Factors/*metabolism
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - beta-Galactosidase/metabolism
PMC - PMC5386468
COIS- The authors declare no conflict of interest.
EDAT- 2017/02/10 06:00
MHDA- 2017/11/01 06:00
PMCR- 2017/02/01
CRDT- 2017/02/10 06:00
PHST- 2016/06/23 00:00 [received]
PHST- 2016/11/21 00:00 [revised]
PHST- 2016/11/29 00:00 [accepted]
PHST- 2017/02/10 06:00 [entrez]
PHST- 2017/02/10 06:00 [pubmed]
PHST- 2017/11/01 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - cddis20171 [pii]
AID - 10.1038/cddis.2017.1 [doi]
PST - epublish
SO  - Cell Death Dis. 2017 Feb 9;8(2):e2607. doi: 10.1038/cddis.2017.1.