» Articles » PMID: 28808304

Hypoxia-induced TET1 Facilitates Trophoblast Cell Migration and Invasion Through HIF1α Signaling Pathway

Overview
Journal Sci Rep
Specialty Science
Date 2017 Aug 16
PMID 28808304
Citations 18
Authors
Affiliations
Soon will be listed here.
Abstract

Low oxygen is a typical extrinsic factor for the regulation of trophoblast biological function, including cell migration, invasion and proliferation. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1), an enzyme converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), is transcriptionally activated by hypoxia in cancer cells. Therefore, we focus on the role of TET1 on trophoblast function in a physiologically hypoxic environment (3% oxygen), which is related to early placentation. Here, we found that TET1 was highly expressed in first trimester villi compared with normal term placentas. In vitro, both TET1 mRNA and protein expression levels in JEG3 cells were increased following exposure to 3% oxygen, and the migration and invasion capacities of JEG3 cells were up-regulated. Furthermore, TET1 knockdown decreased the migration, invasion and proliferation of JEG3 cells exposed to 3% oxygen, and the expression of HIF1α and its downstream target genes was also decreased, which was related to hyper-methylation of the HIF1α promoter. Finally, increased HIF1α protein expression reversed the inhibitory effect of TET1 knockdown on the migration and invasion of JEG3 cells exposed to 3% oxygen. These data show that hypoxia-induced TET1 expression facilitates trophoblast cell migration and invasion through the HIF1α signaling pathway, which plays an important role during placentation.

Citing Articles

Mesenchymal stem cells modulate breast cancer progression through their secretome by downregulating ten-eleven translocation 1.

Motamed R, Jabbari K, Sheikhbahaei M, Ghazimoradi M, Ghodsi S, Jahangir M Sci Rep. 2025; 15(1):6593.

PMID: 39994414 PMC: 11850621. DOI: 10.1038/s41598-025-91314-3.


Simulated ischaemia/reperfusion impairs trophoblast function through divergent oxidative stress- and MMP-9-dependent mechanisms.

Barron A, Tuulari J, Karlsson L, Karlsson H, OKeeffe G, McCarthy C Biosci Rep. 2024; 44(11).

PMID: 39474810 PMC: 11581840. DOI: 10.1042/BSR20240763.


Cx40 Levels Regulate Hypoxia-Induced Changes in the Migration, Proliferation, and Formation of Gap Junction Plaques in an Extravillous Trophoblast Cell Model.

Rozas-Villanueva F, Orellana V, Alarcon R, Maripillan J, Martinez A, Alfaro I Cells. 2024; 13(13.

PMID: 38995001 PMC: 11240472. DOI: 10.3390/cells13131150.


The landscape of implantation and placentation: deciphering the function of dynamic RNA methylation at the maternal-fetal interface.

Wu S, Xie H, Su Y, Jia X, Mi Y, Jia Y Front Endocrinol (Lausanne). 2023; 14:1205408.

PMID: 37720526 PMC: 10499623. DOI: 10.3389/fendo.2023.1205408.


CoCl-mimicked Hypoxia Induces the Assembly of Stress Granules in Trophoblast Cells eIF2α Phosphorylation-dependent and - Independent Pathways.

Ma C, Lv Q, Ma L, Xing B, Li Y, Li Z Curr Mol Med. 2023; 24(10):1291-1300.

PMID: 37711098 DOI: 10.2174/1566524023666230913111300.


References
1.
Shahrzad S, Bertrand K, Minhas K, Coomber B . Induction of DNA hypomethylation by tumor hypoxia. Epigenetics. 2007; 2(2):119-25. DOI: 10.4161/epi.2.2.4613. View

2.
Burton G, Caniggia I . Hypoxia: implications for implantation to delivery-a workshop report. Placenta. 2001; 22 Suppl A:S63-5. DOI: 10.1053/plac.2001.0642. View

3.
Jaakkola P, Mole D, Tian Y, Wilson M, Gielbert J, Gaskell S . Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science. 2001; 292(5516):468-72. DOI: 10.1126/science.1059796. View

4.
Mariani C, Vasanthakumar A, Madzo J, Yesilkanal A, Bhagat T, Yu Y . TET1-mediated hydroxymethylation facilitates hypoxic gene induction in neuroblastoma. Cell Rep. 2014; 7(5):1343-1352. PMC: 4516227. DOI: 10.1016/j.celrep.2014.04.040. View

5.
Williams K, Christensen J, Pedersen M, Johansen J, Cloos P, Rappsilber J . TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature. 2011; 473(7347):343-8. PMC: 3408592. DOI: 10.1038/nature10066. View