Hypoxia Regulates the Expression of PHLDA2 in Primary Term Human Trophoblasts

Kim, H.-S.; Roh, Cheong‐Rae; Chen, B.; Tycko, Benjamin; Nelson, D. Michael; Sadovsky, Yoel

doi:10.1016/j.placenta.2006.01.025

Cited by 22 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TSSC3, also known as PHLDA2, is an imprinted gene [ 32 ]. Genomic imprinting has been reported to contribute to tumorigenesis by predisposing individuals to cancer [ 33 ]; this is mainly regulated by epigenetics [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway

et al. 2017

View full text Add to dashboard Cite

Osteosarcoma is the most common type of bone cancer, and the second leading cause of cancer-related death in children and young adults. Osteosarcoma stem cells are essential for osteosarcoma initiation, metastasis, chemoresistance and recurrence. In the present study, we report that: 1) higher TSSC3 expression indicates a better prognosis for osteosarcoma patients, and; 2) overexpression of TSSC3 significantly decreases sphere-forming capacity, tumor initiation, stemness-related surface markers and Nanog expression in osteosarcoma cells. We also discovered that higher Nanog expression correlates to a worse prognosis for osteosarcoma patients, and overexpression of Nanog increases the stem-related phenotype in osteosarcoma cells. Knockdown of Nanog suppresses these phenotypes. Inhibition of Nanog expression and self-renewal of osteosarcoma cells by TSSC3 overexpression appears to be mediated through inactivation of the Src/Akt pathway. In the clinical setting, expression of TSSC3, p-Src and Nanog is associated with recurrence, metastasis and surgical intervention. Lower TSSC3 expression, higher Nanog expression or higher p-Src expression indicate a poor prognosis for osteosarcoma patients. Overall, our study demonstrates that TSSC3 inhibits the stem-like phenotype and Nanog expression by inactivation of the Src/Akt pathway; this emphasizes the importance of Nanog in osteosarcoma stem cells.

show abstract

Section: Discussionmentioning

confidence: 99%

TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although no previous study has examined placental PHLDA2 expression in relation to sampling site, a number of studies have similarly reported significant intraplacental variation in gene expression [12–14,16,17] . Given that placental PHLDA2 expression is altered in response to hypoxia [31–33] , it is possible that differences in perfusion between distal sites and sites close to the umbilical cord [14,16] could underlie the differences in expression observed. The finding of intraplacental variation in PHLDA2 expression is novel and has implications for interpretation of previous studies and for future studies with consistency in placental sampling of key importance.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, a number of studies have reported differences in gene expression between labouring and non-labouring placentas [26–29] , which may arise from a decrease in placental oxygen supply during contractions [10] and/or differences in exposure to hormones associated with labour [30] . PHLDA2 is known to be responsive to hypoxia [31–33] but it is not known whether placental expression of PHLDA2 , CDKN1C , PEG3 or PEG10 is altered in response to labour.…”

Section: Introductionmentioning

confidence: 99%

Placental expression of imprinted genes varies with sampling site and mode of delivery

Janssen¹,

Tunster²,

Savory³

et al. 2015

Placenta

View full text Add to dashboard Cite

Imprinted genes, which are monoallelically expressed by virtue of an epigenetic process initiated in the germline, are known to play key roles in regulating fetal growth and placental development. Numerous studies are investigating the expression of these imprinted genes in the human placenta in relation to common complications of pregnancy such as fetal growth restriction and preeclampsia. This study aimed to determine whether placental sampling protocols or other factors such as fetal sex, gestational age and mode of delivery may influence the expression of imprinted genes predicted to regulate placental signalling.MethodsTerm placentas were collected from Caucasian women delivering at University Hospital of Wales or Royal Gwent Hospital within two hours of delivery. Expression of the imprinted genes PHLDA2, CDKN1C, PEG3 and PEG10 was assayed by quantitative real time PCR. Intraplacental gene expression was analysed (N = 5). Placental gene expression was compared between male (N = 11) and female (N = 11) infants, early term (N = 8) and late term (N = 10) deliveries and between labouring (N = 13) and non-labouring (N = 21) participants.ResultsThe paternally expressed imprinted genes PEG3 and PEG10 were resilient to differences in sampling site, fetal sex, term gestational age and mode of delivery. The maternally expressed imprinted gene CDKN1C was elevated over 2-fold (p < 0.001) in placenta from labouring deliveries compared with elective caesarean sections. In addition, the maternally expressed imprinted gene PHLDA2 was elevated by 1.8 fold (p = 0.01) in samples taken at the distal edge of the placenta compared to the cord insertion site.ConclusionThese findings support the reinterpretation of existing data sets on these genes in relation to complications of pregnancy and further reinforce the importance of optimising and unifying placental collection protocols for future studies.

show abstract

“…These abnormalities contribute to attenuated uteroplacental perfusion and reduced oxygen transport to the feto-placental unit [5]. In addition to the well-characterized histological changes of injured trophoblasts [4,6], hypoxia influences the repertoire of trophoblast transcripts [7][8][9], with some of these effects attributed to the action of the transcription factor hypoxia inducible factor-1α (HIF1α).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Enhances the Expression of Follistatin-like 3 in Term Human Trophoblasts

et al. 2008

Self Cite

View full text Add to dashboard Cite

Hypoxic injury hinders placental differentiation and alters trophoblast gene expression. We tested the hypothesis that the expression of follistatin-like 3 (FSTL3), a member of the follistatin family of proteins, is modulated by hypoxia in primary human trophoblast (PHT). Using immunofluorescence of human term placental villi we detected the expression of FSTL3 protein in placental villi, primarily in trophoblasts. We verified this finding in cultured term PHT cells. Basal expression of FSTL3 transcript in cultured PHT cells, determined using quantitative PCR, was stable over the culture period. Importantly, when compared to culture in FiO(2)=20% or FiO(2)=8%, PHT cells cultured in FiO(2) <1% exhibited a 4-6 fold increase in FSTL3 mRNA expression as early as 4h in hypoxia. Whereas cellular FSTL3 protein was unchanged in hypoxia, we found that hypoxia increased the level of FSTL3 in the medium. Lastly, the exposure of PHT cells to either the hypoxia-mimetic cobalt chloride or the proline hydroxylase inhibitor dimethyloxaloylglycine upregulated the expression of FSTL3 transcript. Our data indicate that hypoxia enhances the expression of FSTL3 and its release from PHT cells. Our finding that hypoxia-mimetic agents enhance FSTL3 expression implicates HIF1alpha in this process.

show abstract

Hypoxia Regulates the Expression of PHLDA2 in Primary Term Human Trophoblasts

Cited by 22 publications

References 53 publications

TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway

TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway

Placental expression of imprinted genes varies with sampling site and mode of delivery

Hypoxia Enhances the Expression of Follistatin-like 3 in Term Human Trophoblasts

Contact Info

Product

Resources

About