PMID- 31061665
OWN - NLM
STAT- MEDLINE
DCOM- 20190517
LR  - 20220408
IS  - 1689-1392 (Electronic)
IS  - 1425-8153 (Print)
IS  - 1425-8153 (Linking)
VI  - 24
DP  - 2019
TI  - MiR-200c downregulates HIF-1alpha and inhibits migration of lung cancer cells.
PG  - 28
LID - 10.1186/s11658-019-0152-2 [doi]
LID - 28
AB  - BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor with a 
      pivotal role in physiological and pathological responses to hypoxia. While HIF-1alpha 
      is known to be involved in hypoxia-induced upregulation of microRNA (miRNA) 
      expression, HIF-1alpha is also targeted by miRNAs. In this study, miRNAs targeting 
      HIF-1alpha were identified and their effects on its expression and downstream target 
      genes under hypoxic conditions were investigated. Cell migration under the same 
      conditions was also assessed. METHODS: microRNAs that target HIF-1alpha were screened 
      using 3'-untranslated region luciferase (3'-UTR-luciferase) reporter assays. The 
      expression levels of HIF-1alpha and its downstream target genes after transfection 
      with miRNA were assessed using quantitative RT-PCR and western blot analyses. The 
      effect of the miRNAs on the transcriptional activity of HIF-1alpha was determined 
      using hypoxia-responsive element luciferase (HRE-luciferase) assays. Cell 
      migration under hypoxia was examined using the wound-healing assay. RESULTS: 
      Several of the 19 screened miRNAs considerably decreased the luciferase activity. 
      Transfection with miR-200c had substantial impact on the expression level and 
      transcription activity of HIF-1alpha. The mRNA level of HIF-1alpha downstream genes 
      decreased in response to miR-200c overexpression. MiR-200c inhibited cell 
      migration in normoxia and, to a greater extent, in hypoxia. These effects were 
      partly reversed by HIF-1alpha expression under hypoxic conditions. CONCLUSION: 
      miR-200c negatively affects hypoxia-induced responses by downregulating HIF-1alpha, a 
      key regulator of hypoxia. Therefore, overexpression of miR-200c might have 
      therapeutic potential as an anticancer agent that inhibits tumor hypoxia.
FAU - Byun, Yuree
AU  - Byun Y
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
FAU - Choi, Young-Chul
AU  - Choi YC
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
FAU - Jeong, Yunhui
AU  - Jeong Y
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
FAU - Lee, Gangtae
AU  - Lee G
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
FAU - Yoon, Sena
AU  - Yoon S
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
FAU - Jeong, Yongsu
AU  - Jeong Y
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
FAU - Yoon, Jaeseung
AU  - Yoon J
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
FAU - Baek, Kwanghee
AU  - Baek K
AD  - Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of 
      Korea. ISNI: 0000 0001 2171 7818. GRID: grid.289247.2
LA  - eng
PT  - Journal Article
DEP - 20190427
PL  - England
TA  - Cell Mol Biol Lett
JT  - Cellular & molecular biology letters
JID - 9607427
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN200 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Base Sequence
MH  - Cell Hypoxia/genetics
MH  - Cell Line, Tumor
MH  - Cell Movement/*genetics
MH  - DNA Methylation/genetics
MH  - Down-Regulation/*genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Reporter
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism
MH  - Luciferases/metabolism
MH  - Lung Neoplasms/*genetics/*pathology
MH  - MicroRNAs/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcription, Genetic
MH  - Up-Regulation/genetics
MH  - Wound Healing
PMC - PMC6487019
OTO - NOTNLM
OT  - HIF-1alpha
OT  - Hypoxia
OT  - miR-200c
OT  - microRNA
COIS- Not applicable.Not applicable.The authors declare that they have no competing 
      interests.Springer Nature remains neutral with regard to jurisdictional claims in 
      published maps and institutional affiliations.
EDAT- 2019/05/08 06:00
MHDA- 2019/05/18 06:00
PMCR- 2019/04/27
CRDT- 2019/05/08 06:00
PHST- 2018/11/02 00:00 [received]
PHST- 2019/04/03 00:00 [accepted]
PHST- 2019/05/08 06:00 [entrez]
PHST- 2019/05/08 06:00 [pubmed]
PHST- 2019/05/18 06:00 [medline]
PHST- 2019/04/27 00:00 [pmc-release]
AID - 152 [pii]
AID - 10.1186/s11658-019-0152-2 [doi]
PST - epublish
SO  - Cell Mol Biol Lett. 2019 Apr 27;24:28. doi: 10.1186/s11658-019-0152-2. 
      eCollection 2019.