The expression of the imprinted gene pleckstrin homology‐like domain family A member 2 in placental tissues of preeclampsia and its effects on the proliferation, migration and invasion of trophoblast cells JEG‐3

Abstract

Preeclampsia (PE) is one of the most common hypertensive disorders and is a leading cause of morbidity and mortality for pregnant women and perinatal babies. Additionally, pleckstrin homology-like domain family A member 2 (PHLDA2) is associated with placental dysfunction. However, the effect of PHLDA2 on trophoblast cell proliferation, migration and invasion has not been investigated. In this study, 15 PE patients and 15 normal pregnant women were recruited and clinical characteristics were summarized. Pleckstrin homology-like domain family A member 2 levels in placental tissues were examined using real-time PCR and western blot. Overexpression plasmid and PHLDA2 siRNA was introduced into JEG-3 cells, respectively. Cell proliferation was measured using MTT assay and flow cytometry. Cell migration and invasion capacities were assessed by wound healing and Transwell assays. It was found that PE patients collectively presented proteinuria, elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP), and lower gestational ages and birth weights. Pleckstrin homology-like domain family A member 2 levels in the preeclamptic placenta were significantly upregulated. Pleckstrin homology-like domain family A member 2 overexpression significantly arrested cells in the G0/G1 phase, inhibited cell proliferation and suppressed the migration and invasion of JEG-3 cells. Pleckstrin homology-like domain family A member 2 knockdown significantly blocked the cells in the S phase of the cell cycle. Knockdown of PHLDA2 alleviated the inhibition on the migration and invasion of trophoblast cells JEG-3. These findings illustrate that PHLDA2 may participate in PE pathogenesis and indicate its potential application in the early diagnosis of PE.

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes

“…PHLDA2 was found to be highly overexpressed in placentas from preeclamptic pregnancies [107]. The phenotype of female mice carrying fetuses with loss-of-function of Phlda2 has not been reported, but overexpression of PHLDA2 in a human placental cell line resulted in impaired cell proliferation, migration, and invasion [107]. Placental PHLDA2 expression may also be important in preeclampsia.…”

Avaliação do perfil de expressão imuno-histoquímica dos membros da família PHLDA (Pleckstrin homology like domain family A) e potencial valor prognóstico em câncer de mama

“…A proteína codificada pelo gene PHLDA2 pode desempenhar diferentes papéis biológicos específicos de tipo celular e tecidual. Muitas evidências experimentais implicam a expressão de PHLDA2 na indução da apoptose, pelo aumento da liberação de inúmeros componentes mitocôndrias e pela inibição da atividade de membros da superfamília de receptores do fator de necrose tumoral (DAI et al, 2012;HUANG;GUO, 2012;JIN et al, 2016;LEE;FEINBERG, 1998;LI et al, 2014b), além disso, também foi relatado no controle da progressão do ciclo celular (JIN et al, 2015(JIN et al, , 2016WANG et al, 2016). A perda de expressão de PHLDA2 tem sido associada com aumento da motilidade e invasividade em determinadas linhagens tumorais, particularmente pela promoção da EMT via sinalização WNT (int/Wingless family) (LV et al, 2016).…”

“…O gene PHLDA2 diferentemente de seus parálogos da família PHLDA, exibe expressão monoalélica com expressão preferencial do alelo materno, descrito como o primeiro gene pro-apoptótico regulado por imprinting genômico (FRANK et al, 1999;LEE;FEINBERG, 1998). Muitos estudos tem mostrado a implicação da expressão de PHLDA2 para indução de apoptose (DAI et al, 2012;JIN et al, 2016;LI et al, 2014b) e como regulador da progressão do ciclo celular (JIN et al, 2015(JIN et al, , 2016. Alterações no padrão de expressão desta proteína já foram relatadas na promoção da EMT (LV et al, 2016).…”