PMID- 25077652
OWN - NLM
STAT- MEDLINE
DCOM- 20150622
LR  - 20211021
IS  - 1877-8755 (Electronic)
IS  - 1138-7548 (Linking)
VI  - 70
IP  - 3
DP  - 2014 Sep
TI  - Let-7f microRNA negatively regulates hepatic differentiation of human adipose 
      tissue-derived stem cells.
PG  - 781-9
LID - 10.1007/s13105-014-0346-z [doi]
AB  - MicroRNAs (miRNAs) are noncoding RNAs involved in the regulation of the diverse 
      biological processes such as metabolism, proliferation, and cell cycle, in 
      addition to regulation of differentiation. So far, some miRNAs have been 
      recognized to have important role in regulating hepatic functions. Statistically, 
      let-7f has been revealed as a negative regulator of hepatic differentiation. In 
      the present study, we investigated the effect of let-7f on hepatic 
      differentiation of human adipose tissue-derived stem cells (hADSCs). hADSCs were 
      transduced with recombinant lentivirus containing human inhibitor let-7 f. The 
      expression of hepatocyte nuclear factors alpha (HNF4a), albumin (ALB), alpha 
      fetoprotein (AFP), cytokeratin 18 (CK18), and cytokeratin 19 (CK19) was evaluated 
      using quantitative real-time PCR (qRT-PCR). Immunocytochemistry was used to 
      investigate the expression levels of the hepatocyte markers including ALB, AFP, 
      and HNF4a, and biochemical analysis was implemented for hepatic function, 
      glycogen deposition, and urea secretion. qRT-PCR showed significant upregulation 
      in HNF4a, ALB, AFP, CK18, and CK19 expression in cells transduced with let-7f 
      inhibitor lentiviruses. Moreover, positive staining was detected for ALB, AFP, 
      and HNF4a using immunocytochemistry. Urea production and glycogen deposits were 
      also found in the treated cells, the two specific features of the hepatic cells. 
      Therefore, let-7f silencing led to the increased expression of the 
      hepatocyte-specific factors and the accelerated hADSCs hepatic differentiation. 
      Summing all these finding together, our present report has provided evidences 
      that inhibition of let-7f would facilitate induction of hADSCs into 
      hepatocyte-like cells and possibly in regenerative therapy of the liver disease 
      in a wider spectrum.
FAU - Davoodian, Nahid
AU  - Davoodian N
AD  - Department of Clinical Biochemistry, Faculty of Medical Science, Tarbiat Modares 
      University, Tehran, Iran.
FAU - Lotfi, Abbas S
AU  - Lotfi AS
FAU - Soleimani, Masoud
AU  - Soleimani M
FAU - Mola, Seyed Javad
AU  - Mola SJ
FAU - Arjmand, Sare
AU  - Arjmand S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140731
PL  - Spain
TA  - J Physiol Biochem
JT  - Journal of physiology and biochemistry
JID - 9812509
RN  - 0 (Albumins)
RN  - 0 (Biomarkers)
RN  - 0 (HNF4A protein, human)
RN  - 0 (Hepatocyte Nuclear Factor 4)
RN  - 0 (Keratin-18)
RN  - 0 (Keratin-19)
RN  - 0 (MicroRNAs)
RN  - 0 (alpha-Fetoproteins)
RN  - 0 (mirnlet7 microRNA, human)
SB  - IM
MH  - Adipose Tissue/*cytology/*metabolism
MH  - Albumins/genetics/metabolism
MH  - Biomarkers/metabolism
MH  - Cell Differentiation/genetics/physiology
MH  - Gene Silencing
MH  - Hepatocyte Nuclear Factor 4/genetics/metabolism
MH  - Hepatocytes/*cytology/*metabolism
MH  - Humans
MH  - Keratin-18/genetics/metabolism
MH  - Keratin-19/genetics/metabolism
MH  - Mesenchymal Stem Cells/*cytology/*metabolism
MH  - MicroRNAs/antagonists & inhibitors/*genetics/*metabolism
MH  - Up-Regulation
MH  - alpha-Fetoproteins/genetics/metabolism
EDAT- 2014/08/01 06:00
MHDA- 2015/06/24 06:00
CRDT- 2014/08/01 06:00
PHST- 2014/03/31 00:00 [received]
PHST- 2014/07/08 00:00 [accepted]
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/06/24 06:00 [medline]
AID - 10.1007/s13105-014-0346-z [doi]
PST - ppublish
SO  - J Physiol Biochem. 2014 Sep;70(3):781-9. doi: 10.1007/s13105-014-0346-z. Epub 
      2014 Jul 31.