PMID- 32605105
OWN - NLM
STAT- MEDLINE
DCOM- 20210224
LR  - 20211204
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 12
IP  - 7
DP  - 2020 Jun 27
TI  - microRNA-99a Restricts Replication of Hepatitis C Virus by Targeting mTOR and de 
      novo Lipogenesis.
LID - 10.3390/v12070696 [doi]
LID - 696
AB  - In this study, we investigated the role of microRNA-99a (miR-99a) in hepatitis C 
      virus (HCV) replication and lipogenesis in hepatocytes. Cell-culture-derived HCV 
      (HCVcc) infection caused down-regulation of miR-99a in Huh-7 cells, and the 
      relative levels of miR-99a were significantly lower in the sera of the 
      HCV-infected patients than in those of healthy controls. Transfection of 
      miR-99a-5p mimics resulted in a decrease in the intracellular and secreted HCV 
      RNA levels. It also caused a decreased mammalian target of rapamycin (mTOR) 
      protein level and phosphorylation of its downstream targets in HCV-replicating 
      cells. Sterol regulatory element binding protein (SREBP)-1c expression and 
      intracellular lipid accumulation decreased when either miR-99a-5p mimics or 
      si-mTOR was transfected in oleic acid-treated Huh-7 cells. Overexpression of mTOR 
      rescued HCV RNA replication and lipid droplet accumulation in miR-99a-5p 
      mimics-transfected HCV replicon cells. Our data demonstrated that miR-99a 
      ameliorates intracellular lipid accumulation by regulating mTOR/SREBP-1c and 
      causes inefficient replication and packaging of intracellular HCV.
FAU - Lee, Eun Byul
AU  - Lee EB
AD  - The Catholic University Liver Research Center, College of Medicine, The Catholic 
      University of Korea, Seoul 06591, Korea.
FAU - Sung, Pil Soo
AU  - Sung PS
AD  - The Catholic University Liver Research Center, College of Medicine, The Catholic 
      University of Korea, Seoul 06591, Korea.
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 
      Seoul 06591, Korea.
FAU - Kim, Jung-Hee
AU  - Kim JH
AD  - The Catholic University Liver Research Center, College of Medicine, The Catholic 
      University of Korea, Seoul 06591, Korea.
FAU - Park, Dong Jun
AU  - Park DJ
AD  - The Catholic University Liver Research Center, College of Medicine, The Catholic 
      University of Korea, Seoul 06591, Korea.
FAU - Hur, Wonhee
AU  - Hur W
AD  - The Catholic University Liver Research Center, College of Medicine, The Catholic 
      University of Korea, Seoul 06591, Korea.
FAU - Yoon, Seung Kew
AU  - Yoon SK
AD  - The Catholic University Liver Research Center, College of Medicine, The Catholic 
      University of Korea, Seoul 06591, Korea.
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 
      Seoul 06591, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200627
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (MIRN99 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Gene Expression Regulation
MH  - Hepacivirus/genetics/*physiology
MH  - Hepatocytes/virology
MH  - Humans
MH  - Lipogenesis/*genetics
MH  - MicroRNAs/blood/*genetics
MH  - Signal Transduction
MH  - Sterol Regulatory Element Binding Protein 1/genetics
MH  - TOR Serine-Threonine Kinases/*genetics
MH  - Virus Replication/*genetics
PMC - PMC7411587
OTO - NOTNLM
OT  - hepatitis C virus
OT  - lipid droplet
OT  - mTOR
OT  - microRNA-99a
OT  - viral replication
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as potential 
      conflicts of interest.
EDAT- 2020/07/02 06:00
MHDA- 2021/02/25 06:00
PMCR- 2020/07/01
CRDT- 2020/07/02 06:00
PHST- 2020/05/28 00:00 [received]
PHST- 2020/06/22 00:00 [revised]
PHST- 2020/06/24 00:00 [accepted]
PHST- 2020/07/02 06:00 [entrez]
PHST- 2020/07/02 06:00 [pubmed]
PHST- 2021/02/25 06:00 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - v12070696 [pii]
AID - viruses-12-00696 [pii]
AID - 10.3390/v12070696 [doi]
PST - epublish
SO  - Viruses. 2020 Jun 27;12(7):696. doi: 10.3390/v12070696.