PMID- 25496461
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20181202
IS  - 1520-5851 (Electronic)
IS  - 0013-936X (Linking)
VI  - 49
IP  - 2
DP  - 2015 Jan 20
TI  - Evidence for microRNA-mediated regulation of steroidogenesis by hypoxia.
PG  - 1138-47
AB  - Environmental hypoxia can occur in both natural and occupational environments. 
      Over the recent years, the ability of hypoxia to cause endocrine disruption via 
      perturbations in steroid synthesis (steroidogenesis) has become increasingly 
      clear. To further understand the molecular mechanism underlying hypoxia-induced 
      endocrine disruption, the steroid-producing human cell line H295R was used to 
      identify microRNAs (miRNAs) affecting steroidogenic gene expression under 
      hypoxia. Hypoxic treatment of H295R cells resulted in the downregulation of seven 
      steroidogenic genes and one of these, CYP19A1 (aromatase), was shown to be 
      regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). Using 
      bioinformatic and luciferase reporter analyses, miR-98 was identified to be a 
      CYP19A1-targeting miRNA from a subset of HIF-1-inducible miRNAs. Gain- and 
      loss-of-function analysis suggested that under hypoxia, the increased expression 
      of miR-98 led to the downregulation of CYP19A1 mRNA and protein expression and 
      that it may have contributed to a reduction in estradiol (E2) production. 
      Intriguingly, luciferase reporter assays using deletion constructs of a proximal 
      5'-flanking region of miR-98 did not reveal a hypoxia-responsive element 
      (HRE)-containing promoter. Overall, this study provided evidence for the role of 
      miRNAs in regulating steroidogenesis and novel insights into the molecular 
      mechanisms of hypoxia-induced endocrine disruption.
FAU - Yu, Richard Man Kit
AU  - Yu RM
FAU - Chaturvedi, Gayathri
AU  - Chaturvedi G
FAU - Tong, Steve Kwan Hok
AU  - Tong SK
FAU - Nusrin, Suraia
AU  - Nusrin S
FAU - Giesy, John Paul
AU  - Giesy JP
FAU - Wu, Rudolf Shiu Sun
AU  - Wu RS
FAU - Kong, Richard Yuen Chong
AU  - Kong RY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Sci Technol
JT  - Environmental science & technology
JID - 0213155
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Estrogens)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN98 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
RN  - 0 (Steroids)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 1.14.14.1 (Aromatase)
RN  - EC 1.14.14.1 (CYP19A1 protein, human)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Aromatase/*metabolism
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Down-Regulation
MH  - Estradiol/biosynthesis
MH  - Estrogens/metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - MicroRNAs/*metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Steroids/*biosynthesis
EDAT- 2014/12/17 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/12/16 06:00
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1021/es504676s [doi]
PST - ppublish
SO  - Environ Sci Technol. 2015 Jan 20;49(2):1138-47. doi: 10.1021/es504676s.