PMID- 30511377
OWN - NLM
STAT- MEDLINE
DCOM- 20191008
LR  - 20210816
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 144
IP  - 12
DP  - 2019 Jun 15
TI  - miR-4324-RACGAP1-STAT3-ESR1 feedback loop inhibits proliferation and metastasis 
      of bladder cancer.
PG  - 3043-3055
LID - 10.1002/ijc.32036 [doi]
AB  - Considering the importance of microRNAs (miRNAs) in regulating cellular 
      processes, we performed microarray analysis and revealed miR-4324 as one of the 
      most differentially expressed miRNAs in bladder cancer (BCa). Then, we discovered 
      that miR-4324 was a negative regulator of Rac GTPase activating protein 1 
      (RACGAP1) and that RACGAP1 functioned as an oncogenic protein in BCa. Our studies 
      indicated that ectopic overexpression of miR-4324 in BCa cells significantly 
      suppressed cell proliferation and metastasis and enhanced chemotherapy 
      sensitivity to doxorubicin by repressing RACGAP1 expression. Further studies 
      showed that estrogen receptor 1 (ESR1) increased the expression of miR-4324 by 
      binding to its promoter, while the downregulation of ESR1 in BCa was caused by 
      hypermethylation of its promoter. p-STAT3 induced the enrichment of DNMT3B by 
      binding to the ESR1 promoter and then induced methylation of the ESR1 promoter. 
      In turn, RACGAP1 induced STAT3 phosphorylation, increasing p-STAT3 expression and 
      promoting its translocation to the nucleus. Therefore, the 
      miR-4324-RACGAP1-STAT3-ESR1 feedback loop could be a critical regulator of BCa 
      progression.
CI  - (c) 2018 UICC.
FAU - Ge, Qiangqiang
AU  - Ge Q
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Lu, Mengxin
AU  - Lu M
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Ju, Lingao
AU  - Ju L
AD  - Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 
      Wuhan, China.
AD  - Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China.
FAU - Qian, Kaiyu
AU  - Qian K
AD  - Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 
      Wuhan, China.
AD  - Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China.
FAU - Wang, Gang
AU  - Wang G
AD  - Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 
      Wuhan, China.
AD  - Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China.
AD  - Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Wu, Chin-Lee
AU  - Wu CL
AD  - Department of Urology, Massachusetts General Hospital, Harvard Medical School, 
      Boston, MA, USA.
FAU - Liu, Xuefeng
AU  - Liu X
AD  - Department of Pathology, Lombardi Comprehensive Cancer Center, Georgetown 
      University Medical School, Washington, D.C., USA.
FAU - Xiao, Yu
AU  - Xiao Y
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
AD  - Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 
      Wuhan, China.
AD  - Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China.
AD  - Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 
      China.
FAU - Wang, Xinghuan
AU  - Wang X
AUID- ORCID: 0000-0003-3497-0024
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
AD  - Medical Research Institute, Wuhan University, Wuhan, China.
AD  - Urological Clinical Research Center of Laparoscopy in Hubei Province, Wuhan, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190112
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (mgcRacGAP)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/physiology
MH  - DNA Methylation
MH  - Disease Progression
MH  - Down-Regulation
MH  - Doxorubicin/pharmacology
MH  - Estrogen Receptor alpha/genetics/*metabolism
MH  - Feedback, Physiological
MH  - GTPase-Activating Proteins/biosynthesis/genetics/*metabolism
MH  - Heterografts
MH  - Humans
MH  - Lung Neoplasms/genetics/metabolism/secondary
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - MicroRNAs/genetics/*metabolism
MH  - Neoplasm Metastasis
MH  - Promoter Regions, Genetic
MH  - STAT3 Transcription Factor/genetics/*metabolism
MH  - Urinary Bladder Neoplasms/drug therapy/*metabolism/pathology
OTO - NOTNLM
OT  - RACGAP1
OT  - bladder cancer
OT  - chemo-sensitivity
OT  - hypermethylation
OT  - miR-4324
EDAT- 2018/12/05 06:00
MHDA- 2019/10/09 06:00
CRDT- 2018/12/05 06:00
PHST- 2018/08/19 00:00 [received]
PHST- 2018/11/01 00:00 [revised]
PHST- 2018/11/20 00:00 [accepted]
PHST- 2018/12/05 06:00 [pubmed]
PHST- 2019/10/09 06:00 [medline]
PHST- 2018/12/05 06:00 [entrez]
AID - 10.1002/ijc.32036 [doi]
PST - ppublish
SO  - Int J Cancer. 2019 Jun 15;144(12):3043-3055. doi: 10.1002/ijc.32036. Epub 2019 
      Jan 12.