PMID- 30338914
OWN - NLM
STAT- MEDLINE
DCOM- 20191031
LR  - 20210109
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 22
IP  - 12
DP  - 2018 Dec
TI  - MiR-17 family-mediated regulation of Pknox1 influences hepatic steatosis and 
      insulin signaling.
PG  - 6167-6175
LID - 10.1111/jcmm.13902 [doi]
AB  - The aberrant expression of Pknox1 is associated with hepatic glucose and lipid 
      dysmetabolism status of type 2 diabetes mellitus (T2DM) and nonalcoholic fatty 
      liver disease (NAFLD). However, the underlying mechanism causing Pknox1 
      overexpression in this pathological status remains unclear. By using miRNA target 
      prediction programs, we found that the 3'-UTR of the Pknox1 mRNA sequence 
      contains highly conserved target sites of miR-17 family. In a rat model of 
      streptozotocin and high-fat diet-induced T2DM and NAFLD complication, the 
      increased hepatic expression of Pknox1 was consistent with decreased expressions 
      of miR-17 family, especially miR-17 and miR-20a. Furthermore, an inverse 
      correlation was observed between Pknox1 and miR-17 and miR-20a in free fatty 
      acids-induced hepatocyte steatosis. Dual-luciferase reporter assay further showed 
      that Pknox1 was a valid target gene of miR-17 family. The ectopic expression of 
      miR-17 or miR-20a could markedly suppress Pknox1 expression in hepatocytes. 
      MiR-17 or miR-20a overexpression also resulted in significantly enhanced insulin 
      sensitivity and reduced hepatocyte steatosis in HepG2 and L02 cells, which were 
      determined by altered phosphorylation on insulin receptor signaling pathway 
      proteins and decreased intracellular triglyceride and lipid accumulation, 
      respectively. These data implicate the upregulated hepatic expression of Pknox1 
      in T2DM complicated with NAFLD may be caused by the reduced expression of miR-17 
      family, indicating that developing miRNA-mediated regulation strategies on Pknox1 
      may provide new therapeutic options for metabolic disease.
CI  - (c) 2018 The Authors. Journal of Cellular and Molecular Medicine published by John 
      Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
FAU - Ye, Dan
AU  - Ye D
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Lou, Guohua
AU  - Lou G
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, 
      Collaborative Innovation Center for Diagnosis and Treatament of Infectious 
      Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang 
      University, Hangzhou, China.
FAU - Zhang, Tianbao
AU  - Zhang T
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, 
      Collaborative Innovation Center for Diagnosis and Treatament of Infectious 
      Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang 
      University, Hangzhou, China.
FAU - Dong, Fengqin
AU  - Dong F
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Liu, Yanning
AU  - Liu Y
AUID- ORCID: 0000-0002-0554-6622
AD  - State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, 
      Collaborative Innovation Center for Diagnosis and Treatament of Infectious 
      Diseases, The First Affiliated Hospital of School of Medicine, Zhejiang 
      University, Hangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181019
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Insulin)
RN  - 0 (MIRN17 microRNA, human)
RN  - 0 (MIRN20 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (PKNOX1 protein, human)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Experimental/genetics/metabolism/pathology
MH  - Diabetes Mellitus, Type 2/complications/*genetics/metabolism/pathology
MH  - Fatty Liver/complications/*genetics/metabolism/pathology
MH  - Gene Expression Regulation
MH  - Hep G2 Cells
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - Insulin/genetics
MH  - MicroRNAs/*genetics
MH  - Non-alcoholic Fatty Liver Disease/complications/*genetics/pathology
MH  - Rats
MH  - Signal Transduction/genetics
PMC - PMC6237553
OTO - NOTNLM
OT  - Pknox1
OT  - hepatocyte steatosis
OT  - insulin resistance
OT  - metabolic disease
OT  - miR-17 family
EDAT- 2018/10/20 06:00
MHDA- 2019/11/02 06:00
PMCR- 2018/12/01
CRDT- 2018/10/20 06:00
PHST- 2018/04/09 00:00 [received]
PHST- 2018/08/16 00:00 [accepted]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2019/11/02 06:00 [medline]
PHST- 2018/10/20 06:00 [entrez]
PHST- 2018/12/01 00:00 [pmc-release]
AID - JCMM13902 [pii]
AID - 10.1111/jcmm.13902 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2018 Dec;22(12):6167-6175. doi: 10.1111/jcmm.13902. Epub 2018 Oct 
      19.