PMID- 36934412
OWN - NLM
STAT- MEDLINE
DCOM- 20230407
LR  - 20230407
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 47
IP  - 5
DP  - 2023 May
TI  - MicroRNA-17-3p protects against excessive posthypoxic autophagy in H9C2 
      cardiomyocytes via PTEN-Akt-mTOR signaling pathway.
PG  - 943-953
LID - 10.1002/cbin.11999 [doi]
AB  - The activity of phosphatase and tensin homolog (PTEN) can be inhibited by 
      miR-17-3p, which results in attenuating myocardial ischemia/reperfusion injury 
      (IRI), however, the mechanism behind this phenomenon is still elusive. 
      Suppression of PTEN leads to augmented protein kinase B (Akt)/mammalian target of 
      rapamycin (mTOR) signaling strength and constrained autophagy activation, which 
      might be the one mechanism for the ameliorated myocardial IRI. Thus, we tested 
      the hypothesis that miR-17-3p attenuated hypoxia/reoxygenation (H/R)-mediated 
      damage in cardiomyocytes by downregulating excessive autophagy via the 
      PTEN-Akt-mTOR axis. The expression of miR-17-3p was remarkably increased after 
      H/R treatment (6-h hypoxia followed by 6-h reoxygenation; H6/R6), which was 
      concomitant with the increase of the release of lactic acid dehydrogenase (cell 
      injury marker) and the enhancement LC3II/I ratio (autophagy markers) in H9C2 
      cardiomyocytes. Ectoexpression of miR-17-3p agomir led to remarkable augmentation 
      of miR-17-3p expression and evidently attenuated H/R-mediated cell damage and 
      excessive autophagy. Furthermore, an increase in miR-17-3p expression elicited 
      constrained phosphorylation of PTEN (Ser(380) ) while enhanced the 
      phosphorylation of Akt (Thr(308) , Ser(473) ) and mTOR (Ser(536) ) after H/R 
      stimulation. In addition, pretreatment with LY-294002 (an Akt selective 
      inhibitor) and rapamycin (an mTOR selective inhibitor) significantly abrogated 
      the protective function of miR-17-3p on H/R-mediated cell damage and autophagy in 
      H9C2 cardiomyocytes. Taken together, these observations indicated that the 
      enhancement of the PTEN/Akt/mTOR axis and the consequent suppression of autophagy 
      overactivation might represent an underlying mechanism by which miR-17-3p 
      attenuated H/R-mediated damage in H9C2 cells.
CI  - (c) 2023 International Federation for Cell Biology.
FAU - He, Yi
AU  - He Y
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital (Guangdong 
      Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
FAU - Zhang, Dengwen
AU  - Zhang D
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital (Guangdong 
      Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
FAU - Zhang, Qingqing
AU  - Zhang Q
AD  - Guangdong Provincial People's Hospital Ganzhou Hospital, Ganzhou Municipal 
      Hospital, Ganzhou, China.
FAU - Cai, Yin
AU  - Cai Y
AD  - Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
FAU - Huang, Chongfeng
AU  - Huang C
AD  - Guangdong Provincial People's Hospital Ganzhou Hospital, Ganzhou Municipal 
      Hospital, Ganzhou, China.
FAU - Xia, Zhengyuan
AU  - Xia Z
AD  - Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China.
AD  - Department of Anesthesiology, Affiliated Hospital of Guangdong Medical 
      University, Guangdong, China.
FAU - Wang, Sheng
AU  - Wang S
AUID- ORCID: 0000-0002-7864-3589
AD  - Department of Anesthesiology, Guangdong Provincial People's Hospital (Guangdong 
      Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
LA  - eng
GR  - 20221009/Administration of Traditional Chinese Medicine of Guangdong Province/
PT  - Journal Article
DEP - 20230319
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Myocytes, Cardiac/metabolism
MH  - Cell Line
MH  - *MicroRNAs/metabolism
MH  - Apoptosis
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Mammals/metabolism
MH  - Hypoxia/metabolism
MH  - Autophagy
OTO - NOTNLM
OT  - autophagy
OT  - cardiomyocytes
OT  - hypoxia/reoxygenation
OT  - microRNA
OT  - rat
EDAT- 2023/03/20 06:00
MHDA- 2023/04/07 06:42
CRDT- 2023/03/19 14:13
PHST- 2022/12/13 00:00 [revised]
PHST- 2022/07/12 00:00 [received]
PHST- 2023/01/02 00:00 [accepted]
PHST- 2023/04/07 06:42 [medline]
PHST- 2023/03/20 06:00 [pubmed]
PHST- 2023/03/19 14:13 [entrez]
AID - 10.1002/cbin.11999 [doi]
PST - ppublish
SO  - Cell Biol Int. 2023 May;47(5):943-953. doi: 10.1002/cbin.11999. Epub 2023 Mar 19.