PMID- 30302791
OWN - NLM
STAT- MEDLINE
DCOM- 20200318
LR  - 20211204
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 3
DP  - 2019 Mar
TI  - Hypoxia-induced regulation of mTOR signaling by miR-7 targeting REDD1.
PG  - 4523-4532
LID - 10.1002/jcb.27740 [doi]
AB  - Oxygen is an important factor mediating cell growth and survival under 
      physiological and pathological conditions. Therefore, cells have well-regulated 
      response mechanisms in the face of changes in oxygen levels in their environment. 
      A subset of microRNAs (miRNAs) termed the hypoxamir has been suggested to be a 
      critical mediator of the cellular response to hypoxia. Regulated in development 
      and DNA damage response 1 (REDD1) is a negative regulator of mammalian target of 
      rapamycin (mTOR) signaling in the response to cellular stress, and is elevated in 
      many cell types under hypoxia, with consequent inhibition of mTOR signaling. 
      However, the underlying posttranscriptional regulatory mechanism by miRNAs that 
      contribute to this hypoxia-induced reduction in REDD1 expression remain unknown. 
      Therefore, the aim of the current study was to identify the miRNAs participating 
      in the hypoxic cellular response by scanning the 3'-untranslated region (3'-UTR) 
      of REDD1 for potential miRNA-binding sites using a computer algorithm, 
      TargetScan. miR-7 emerged as a novel hypoxamir that regulates REDD1 expression 
      and is involved in mTOR signaling. miR-7 could repress REDD1 expression 
      posttranscriptionally by directly binding with the 3'-UTR. Upon hypoxia, miR-7 
      expression was downregulated in HeLa cells to consequently derepress REDD1, 
      resulting in inhibition of mTOR signaling. Moreover, overexpression of miR-7 was 
      sufficient to reverse the hypoxia-induced inhibition of mTOR signaling. 
      Therefore, our findings suggest miR-7 as a key regulator of hypoxia-mediated mTOR 
      signaling through modulation of REDD1 expression. These findings contribute new 
      insight into the miRNA-mediated molecular mechanism of the hypoxic response 
      through mTOR signaling, highlighting potential targets for tumor suppression.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Seong, Minhyeong
AU  - Seong M
AD  - Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon 
      National University, Incheon, Korea.
FAU - Lee, Jihui
AU  - Lee J
AD  - Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon 
      National University, Incheon, Korea.
FAU - Kang, Hara
AU  - Kang H
AUID- ORCID: 0000-0002-3302-7627
AD  - Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon 
      National University, Incheon, Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181009
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (DDIT4 protein, human)
RN  - 0 (MIRN7 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Hypoxia
MH  - *Gene Expression Regulation
MH  - HeLa Cells
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Transcription Factors/genetics/*metabolism
OTO - NOTNLM
OT  - hypoxia
OT  - mammalian target of rapamycin (mTOR) signaling
OT  - miR-7
OT  - microRNA (miRNA)
OT  - regulated in development and DNA damage response 1 (REDD1)
EDAT- 2018/10/12 06:00
MHDA- 2020/03/19 06:00
CRDT- 2018/10/11 06:00
PHST- 2018/05/21 00:00 [received]
PHST- 2018/08/30 00:00 [accepted]
PHST- 2018/10/12 06:00 [pubmed]
PHST- 2020/03/19 06:00 [medline]
PHST- 2018/10/11 06:00 [entrez]
AID - 10.1002/jcb.27740 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Mar;120(3):4523-4532. doi: 10.1002/jcb.27740. Epub 2018 Oct 
      9.