PMID- 34120306
OWN - NLM
STAT- MEDLINE
DCOM- 20220207
LR  - 20240226
IS  - 1559-0259 (Electronic)
IS  - 1530-7905 (Linking)
VI  - 21
IP  - 9
DP  - 2021 Sep
TI  - MicroRNA-17-5p Promotes Cardiac Hypertrophy by Targeting Mfn2 to Inhibit 
      Autophagy.
PG  - 759-771
LID - 10.1007/s12012-021-09667-w [doi]
AB  - Pathological cardiac hypertrophy is the leading cause of heart failure, and 
      miRNAs have been recognized as key factors in cardiac hypertrophy. This study 
      aimed to elucidate whether miR-17-5p affects cardiac hypertrophy by targeting the 
      mitochondrial fusion protein mitofusin 2 (Mfn2)-mediated 
      phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) 
      pathway and regulating autophagy. miR-17-5p expression was shown to be 
      upregulated both in vivo and in vitro. In addition, a miR-17-5p inhibitor 
      significantly reversed AngII-induced cell hypertrophy in neonatal rat left 
      ventricle myocytes (NRVMs). In contrast to miR-17-5p expression, Mfn2 expression 
      was inhibited in rat hearts at 4 weeks after transverse aortic constriction (TAC) 
      and in an Ang II-induced cell hypertrophy model. We examined miR-17-5p targeting 
      of Mfn2 by dual luciferase reporter and Western blot assays. In addition, we also 
      verified the relationship between Mfn2 and the PI3K/AKT/mTOR pathway. Mfn2 
      overexpression attenuated miR-17-5p-induced cell hypertrophy, and in rat 
      myocardial tissue, miR-17-5p induced autophagy inhibition. In summary, the 
      results of the present study demonstrated that miR-17-5p inhibits Mfn2 
      expression, activates the PI3K/AKT/mTOR pathway and suppresses autophagy to 
      promote cardiac hypertrophy.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Xu, Xuan
AU  - Xu X
AD  - Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 
      226001, Jiangsu, China.
AD  - Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast 
      University, Nanjing, 210009, Jiangsu, China.
FAU - Su, Yi-Ling
AU  - Su YL
AD  - Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 
      226001, Jiangsu, China.
FAU - Shi, Jia-Yu
AU  - Shi JY
AD  - Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 
      226001, Jiangsu, China.
FAU - Lu, Qi
AU  - Lu Q
AD  - Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 
      226001, Jiangsu, China. luqint@sina.com.
FAU - Chen, Chu
AU  - Chen C
AD  - Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, 
      226001, Jiangsu, China. chenchu_xiaoxiao@126.com.
LA  - eng
GR  - no. 2016-WSN-103/Six Talent Peaks Project in Jiangsu Province/
GR  - JC2018082/Nantong Municipal Science and Technology Bureau (CN)/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210612
PL  - United States
TA  - Cardiovasc Toxicol
JT  - Cardiovascular toxicology
JID - 101135818
RN  - 0 (MIRN17 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Mitochondrial Proteins)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.1.- (Mfn2 protein, rat)
SB  - IM
MH  - Angiotensin II/toxicity
MH  - Animals
MH  - *Autophagy/drug effects
MH  - Cardiomegaly/genetics/*metabolism/pathology
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - GTP Phosphohydrolases/genetics/*metabolism
MH  - Gene Expression Regulation
MH  - Male
MH  - MicroRNAs/genetics/*metabolism
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Myocytes, Cardiac/drug effects/*metabolism/pathology
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Rats
OTO - NOTNLM
OT  - Autophagy
OT  - Cardiac hypertrophy
OT  - Mfn2
OT  - MicroRNA-17-5p
OT  - PI3K/AKT/mTOR pathway
EDAT- 2021/06/14 06:00
MHDA- 2022/02/08 06:00
CRDT- 2021/06/13 21:07
PHST- 2020/10/06 00:00 [received]
PHST- 2021/06/03 00:00 [accepted]
PHST- 2021/06/14 06:00 [pubmed]
PHST- 2022/02/08 06:00 [medline]
PHST- 2021/06/13 21:07 [entrez]
AID - 10.1007/s12012-021-09667-w [pii]
AID - 10.1007/s12012-021-09667-w [doi]
PST - ppublish
SO  - Cardiovasc Toxicol. 2021 Sep;21(9):759-771. doi: 10.1007/s12012-021-09667-w. Epub 
      2021 Jun 12.