PMID- 29404451
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2471-254X (Electronic)
IS  - 2471-254X (Linking)
VI  - 1
IP  - 2
DP  - 2017 Apr
TI  - MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting beta-catenin 
      and Wnt signaling.
PG  - 168-183
LID - 10.1002/hep4.1029 [doi]
AB  - Hepatoblastoma (HBL) is the most common pediatric liver cancer. In this malignant 
      neoplasm, beta-catenin protein accumulates and increases Wnt signaling due to 
      recurrent activating mutations in the catenin-beta 1 (CTNNB1) gene. Therefore, 
      beta-catenin is a key therapeutic target in HBL. However, controlling 
      beta-catenin production with therapeutic molecules has been challenging. New 
      biological studies could provide alternative therapeutic solutions for the 
      treatment of HBL, especially for advanced tumors and metastatic disease. In this 
      study, we identified microRNAs (miRNAs) that target beta-catenin and block HBL 
      cell proliferation in vitro and tumor growth in vivo. Using our 
      dual-fluorescence-FunREG system, we screened a library of 1,712 miRNA mimics and 
      selected candidates inhibiting CTNNB1 expression through interaction with its 
      untranslated regions. After validating the regulatory effect of nine miRNAs on 
      beta-catenin in HBL cells, we measured their expression in patient samples. 
      Let-7i-3p, miR-449b-3p, miR-624-5p, and miR-885-5p were decreased in tumors 
      compared to normal livers. Moreover, they inhibited HBL cell growth and Wnt 
      signaling activity in vitro partly through beta-catenin down-regulation. 
      Additionally, miR-624-5p induced cell senescence in vitro, blocked experimental 
      HBL growth in vivo, and directly targeted the beta-catenin 3'-untranslated 
      region. Conclusion: Our results shed light on how beta-catenin-regulating miRNAs 
      control HBL progression through Wnt signaling inactivation. In particular, 
      miR-624-5p may constitute a promising candidate for miRNA replacement therapy for 
      HBL patients. (Hepatology Communications 2017;1:168-183).
FAU - Indersie, Emilie
AU  - Indersie E
AD  - Univ. Bordeaux, Inserm, GREF, U1053, 33076 Bordeaux France.
AD  - Univ. Bordeaux, Inserm, BMGIC, U1035, 33076 Bordeaux France.
FAU - Lesjean, Sarah
AU  - Lesjean S
AD  - Univ. Bordeaux, Inserm, GREF, U1053, 33076 Bordeaux France.
AD  - Univ. Bordeaux, Inserm, BMGIC, U1035, 33076 Bordeaux France.
FAU - Hooks, Katarzyna B
AU  - Hooks KB
AUID- ORCID: 0000-0003-0687-4393
AD  - Univ. Bordeaux, Inserm, GREF, U1053, 33076 Bordeaux France.
AD  - Univ. Bordeaux, Inserm, BMGIC, U1035, 33076 Bordeaux France.
FAU - Sagliocco, Francis
AU  - Sagliocco F
AD  - Univ. Bordeaux, Inserm, GREF, U1053, 33076 Bordeaux France.
AD  - Univ. Bordeaux, Inserm, BMGIC, U1035, 33076 Bordeaux France.
FAU - Ernault, Tony
AU  - Ernault T
AD  - INSERM, UMR 1193, Paul-Brousse Hospital, Hepatobiliary Centre F-94800 Villejuif 
      France.
AD  - Univ. Paris Saclay F-94800 Villejuif France.
FAU - Cairo, Stefano
AU  - Cairo S
AD  - XenTechEvry France.
AD  - Laboratory for Technologies of Advanced Therapies, Department of Morphology, 
      Surgery and Experimental Medicine University of Ferrara Italy.
FAU - Merched-Sauvage, Maria
AU  - Merched-Sauvage M
AD  - Bordeaux University Hospital Bordeaux France.
FAU - Rullier, Anne
AU  - Rullier A
AD  - Bordeaux University Hospital Bordeaux France.
FAU - Le Bail, Brigitte
AU  - Le Bail B
AD  - Bordeaux University Hospital Bordeaux France.
FAU - Taque, Sophie
AU  - Taque S
AD  - Rennes University Hospital Rennes France.
FAU - Grotzer, Michael
AU  - Grotzer M
AD  - SIOPEL (International Childhood Liver Tumours Strategy Group) Liver Tumor and 
      Tissue Banking Program University Children's Hospital Zurich Switzerland.
FAU - Branchereau, Sophie
AU  - Branchereau S
AD  - Bicetre Hospital Le Kremlin-Bicetre France.
FAU - Guettier, Catherine
AU  - Guettier C
AD  - Bicetre Hospital Le Kremlin-Bicetre France.
FAU - Fabre, Monique
AU  - Fabre M
AD  - Necker Hospital Paris France.
FAU - Brugieres, Laurence
AU  - Brugieres L
AD  - Gustave Roussy Cancer Campus Villejuif France.
FAU - Hagedorn, Martin
AU  - Hagedorn M
AD  - Univ. Bordeaux, Inserm, GREF, U1053, 33076 Bordeaux France.
AD  - Univ. Bordeaux, Inserm, BMGIC, U1035, 33076 Bordeaux France.
FAU - Buendia, Marie-Annick
AU  - Buendia MA
AD  - INSERM, UMR 1193, Paul-Brousse Hospital, Hepatobiliary Centre F-94800 Villejuif 
      France.
AD  - Univ. Paris Saclay F-94800 Villejuif France.
FAU - Grosset, Christophe F
AU  - Grosset CF
AD  - Univ. Bordeaux, Inserm, GREF, U1053, 33076 Bordeaux France.
AD  - Univ. Bordeaux, Inserm, BMGIC, U1035, 33076 Bordeaux France.
LA  - eng
PT  - Journal Article
DEP - 20170406
PL  - United States
TA  - Hepatol Commun
JT  - Hepatology communications
JID - 101695860
PMC - PMC5721429
EDAT- 2018/02/07 06:00
MHDA- 2018/02/07 06:01
PMCR- 2017/04/06
CRDT- 2018/02/07 06:00
PHST- 2016/12/22 00:00 [received]
PHST- 2017/01/24 00:00 [revised]
PHST- 2017/02/27 00:00 [accepted]
PHST- 2018/02/07 06:00 [entrez]
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2018/02/07 06:01 [medline]
PHST- 2017/04/06 00:00 [pmc-release]
AID - HEP41029 [pii]
AID - 10.1002/hep4.1029 [doi]
PST - epublish
SO  - Hepatol Commun. 2017 Apr 6;1(2):168-183. doi: 10.1002/hep4.1029. eCollection 2017 
      Apr.