PMID- 29402794
OWN - NLM
STAT- MEDLINE
DCOM- 20180316
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 45
IP  - 1
DP  - 2018
TI  - BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in 
      Micro-Vehicles.
PG  - 366-377
LID - 10.1159/000486908 [doi]
AB  - BACKGROUND/AIMS: Emerging studies on brain-derived neurotrophic factor (BDNF) 
      have shown that might be novel biomarkers and therapeutic targets for cancer. We 
      explore the role of BDNF in the tumorigenesis of bladder cancer and the 
      underlying molecular mechanism. METHODS: 368 patients with diagnosed bladder 
      cancer and 352 healthy controls were enrolled to evaluate the association of BDNF 
      and the miR-146b. Bioinformatics algorithm analysis and luciferase assay were 
      performed to identify the target genes of miR-146b. Real-time PCR and 
      western-blot were carried out to validate the relationship between miR-146b and 
      CRK. MTT assay and FACS were used to evaluated the proliferation and apoptosis of 
      cancer cells. MVs were isolated and transfect into the culture cells to confirm 
      the above observation. RESULTS: The clinical study shows that BDNF Met/Met was 
      significantly associated with the risk of bladder cancer. In addition, comparing 
      with Val/Val and Val/Met, Met/Met has lower miR-146b level. Luciferase assay 
      shows that BDNF Val/Val is apparently enhanced miR-146b promoter-luciferase, but 
      not BDNF Met/Met. Based on luciferase assay, CRK is a direct target gene of 
      miR-146b. MiR-146b mimics significantly inhibited the expression of CRK and 
      activation of AKT level. The expression of CRK and the activation of AKT (p-AKT) 
      were significantly inhibited by MV-BDNF Val/Val-miR-146b or MV-BDNF 
      Val/Met-miR-146b, but not MV-BDNF Met/Met-miR-146b. MV-BDNF Val/Val-miR-146b or 
      Val/Met-miR-146b obviously inhibited cell proliferation, which eliminated by CRK. 
      Meanwhile, with MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not affect 
      the proliferation. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b enhanced cell 
      apoptosis, which could be eliminated by CRK. Meanwhile, MV-BDNF Met/Met-miR-146b 
      or Met/Met-miR-146b+CRK did not promote apoptosis. CONCLUSION: BDNF VAL66MET 
      polymorphism is associated with miR-146b and its target gene CRK. MiR-146b and 
      CRK mediated BDNF VAL66MET polymorphism associated proliferation and apoptosis 
      via activation of AKT. Thus, BDNF Val66Met is associated with the risk of bladder 
      cancer, and the BDNF variant could be used a biomarker for the diagnosis of 
      bladder cancer.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Li, Cong
AU  - Li C
FAU - Zeng, Xing
AU  - Zeng X
FAU - Liu, Zheng
AU  - Liu Z
FAU - Li, Fan
AU  - Li F
FAU - Wang, Kun
AU  - Wang K
FAU - Wu, Baisen
AU  - Wu B
LA  - eng
PT  - Journal Article
DEP - 20180122
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Antagomirs)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (IGFBP5-interacting protein, human)
RN  - 0 (MIRN146 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proto-Oncogene Proteins c-crk)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Aged
MH  - Antagomirs/metabolism
MH  - Apoptosis
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism
MH  - Carrier Proteins/antagonists & inhibitors/genetics/metabolism
MH  - Cell Proliferation
MH  - Female
MH  - Gene Frequency
MH  - Genotype
MH  - Humans
MH  - Male
MH  - MicroRNAs/antagonists & inhibitors/genetics/*metabolism
MH  - Microsomes/metabolism
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - Proto-Oncogene Proteins c-crk/genetics/metabolism
MH  - Risk
MH  - Sequence Alignment
MH  - Urinary Bladder Neoplasms/genetics/metabolism/*pathology
OTO - NOTNLM
OT  - BDNF
OT  - BDNF Val66Met
OT  - Bladder cancer
OT  - CRK
OT  - MiR-146b
OT  - Micro-vesicle
EDAT- 2018/02/07 06:00
MHDA- 2018/03/17 06:00
CRDT- 2018/02/07 06:00
PHST- 2017/04/21 00:00 [received]
PHST- 2017/10/09 00:00 [accepted]
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2018/03/17 06:00 [medline]
PHST- 2018/02/07 06:00 [entrez]
AID - 000486908 [pii]
AID - 10.1159/000486908 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;45(1):366-377. doi: 10.1159/000486908. Epub 2018 Jan 
      22.