PMID- 26935516
OWN - NLM
STAT- MEDLINE
DCOM- 20161226
LR  - 20220408
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 37
IP  - 4
DP  - 2016 Apr
TI  - Lentivirus-mediated PHLDA2 overexpression inhibits trophoblast proliferation, 
      migration and invasion, and induces apoptosis.
PG  - 949-57
LID - 10.3892/ijmm.2016.2508 [doi]
AB  - Inadequate trophoblast invasion and increased trophoblast apoptosis cause serious 
      pregnancy complications. Pleckstrin homology-like domain, family Alpha, member 2 
      (PHLDA2) has been linked to fetal size at birth and growth restriction in a 
      number of studies. However, the impact of PHLDA2 on trophoblast function had not 
      been studied previously, to the best of our knowledge. In the present study, 
      immunofluorescence staining demonstrated that primary trophoblasts isolated from 
      placental villous tissues were positive for cytokeratin 18 (CK18), vimentin and 
      human placental lactogen (hPL). JEG-3 cells and primary trophoblasts were 
      infected with lentivirus overexpressing PHLDA2. RT-qPCR and western blot analysis 
      detected high levels of PHLDA2. A Cell Counting Kit-8 (CCK-8) assay showed that 
      PHLDA2 overexpression inhibited trophoblast proliferation. In addition, PHLDA2 
      significantly induced apoptosis, as evidenced by Annexin V-FITC/propidium iodide 
      (PI) and Hoechst staining, along with activation of Bax and caspase-3 and also 
      decreased Bcl-2 expression. Further investigation showed that PHLDA2 effectively 
      induced reactive oxygen species (ROS) generation, caused cytochrome c release 
      from the mitochondria into the cytosol and decreased mitochondrial membrane 
      potential. PHLDA2 likely induced apoptosis through the mitochondrial pathway. 
      Wound healing and Transwell assays indicated that PHLDA2 overexpression 
      efficiently suppressed cell migration and invasion. These data suggest that 
      PHLDA2 plays an important role in the occurrence and development of pregnancy 
      complications by promoting trophoblast apoptosis and suppressing cell invasion.
FAU - Jin, Feng
AU  - Jin F
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
FAU - Qiao, Chong
AU  - Qiao C
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
FAU - Luan, Nannan
AU  - Luan N
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
FAU - Li, Hui
AU  - Li H
AD  - Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical 
      University, Shenyang, Liaoning 110004, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160226
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Nuclear Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (TSSC3 protein)
SB  - IM
MH  - *Apoptosis
MH  - Cell Line
MH  - Cell Movement
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Female
MH  - Humans
MH  - Lentivirus/genetics
MH  - Membrane Potential, Mitochondrial
MH  - Nuclear Proteins/*genetics/metabolism
MH  - Pregnancy
MH  - Pregnancy Complications/etiology/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Trophoblasts/*cytology/metabolism
MH  - *Up-Regulation
PMC - PMC4790661
EDAT- 2016/03/05 06:00
MHDA- 2016/12/27 06:00
PMCR- 2016/02/26
CRDT- 2016/03/04 06:00
PHST- 2015/07/30 00:00 [received]
PHST- 2016/01/07 00:00 [accepted]
PHST- 2016/03/04 06:00 [entrez]
PHST- 2016/03/05 06:00 [pubmed]
PHST- 2016/12/27 06:00 [medline]
PHST- 2016/02/26 00:00 [pmc-release]
AID - ijmm-37-04-0949 [pii]
AID - 10.3892/ijmm.2016.2508 [doi]
PST - ppublish
SO  - Int J Mol Med. 2016 Apr;37(4):949-57. doi: 10.3892/ijmm.2016.2508. Epub 2016 Feb 
      26.