Proteomic Analysis Reveals That Placenta-Specific Protein 9 Inhibits Proliferation and Stimulates Motility of Human Bronchial Epithelial Cells

Abstract

Placenta-specific protein 9 (PLAC9) is a putative secretory protein that was initially identified in the placenta and is involved in cell proliferation and motility. Bioinformatics analyses revealed that PLAC9 is repressed in lung cancers (LCs), especially lung adenocarcinomas, compared to that in the paired adjacent normal tissues, indicating that PLAC9 might be involved in the pathogenesis of pulmonary diseases. To investigate the potential role of PLAC9 in the abnormal reprogramming of airway epithelial cells (AECs), a key cause of pulmonary diseases, we constructed a stable PLAC9-overexpressing human bronchial epithelial cell line (16HBE-GFP-Plac9). We utilized the proteomic approach isobaric tag for relative and absolute quantification (iTRAQ) to analyze the effect of PLAC9 on cellular protein composition. Gene ontology (GO) and pathway analyses revealed that GO terms and pathways associated with cell proliferation, cell cycle progression, and cell motility and migration were significantly enriched among the proteins regulated by PLAC9. Our in vitro results showed that PLAC9 overexpression reduced cell proliferation, altered cell cycle progression, and increased cell motility, including migration and invasion. Our findings suggest that PLAC9 inhibits cell proliferation through S phase arrest by altering the expression levels of cyclin/cyclin-dependent kinases (CDKs) and promotes cell motility, likely via the concerted actions of cyclins, E-cadherin, and vimentin. Since these mechanisms may underlie PLAC9-mediated abnormal human bronchial pathogenesis, our study provides a basis for the development of molecular targeted treatments for LCs.

Myeloperoxidase-derived hypochlorous acid targets human airway epithelial plasmalogens liberating protein modifying electrophilic 2-chlorofatty aldehydes

“…Seven hundred and twenty-eight proteins were shown to be modified by 2-ClHDyA including those modified by HDyA in HSAEC. A total of 6841 proteins have been reported to be identified in human bronchial epithelial cell [ 54 ]. Thus, about 11% of HSAEC proteins are modified by 2-ClHDyA.…”

Isovalerylspiramycin I suppresses non-small cell lung carcinoma growth through ROS-mediated inhibition of PI3K/AKT signaling pathway

“…Our results showed that ISP-I suppressed cell proliferation associated with G2/M arrest. Activation of the cyclin B1/cdc2 complex is central to facilitate G2/M cell cycle transition, mainly mediated by dephosphorylation of cdc2 [42,43]. P21, as a vital member of CDK inhibitor, suppresses cyclin B1/cdc2 complex activity by interacting with many important proteins, including cdc2 and GADD45A [44], thereby inhibiting the G2/M transition in various cancer types both p53-dependent and p53-independent [45,46].…”

Candidate oncogene placenta specific 8 affect cell growth and cell migration in non- small cell lung cancers

“…Cell counting assays were performed to detect the effects of PLAC8 on cell proliferation as previously described with minor modi cation (15,17). In 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, Sigma, St Louis, MO, USA) assay, the cells were seeded at a density of 2,000 cells/well in 96-well tissue culture plates with 200 µL culture medium.…”

“…Wound healing and invasion assays were performed as previously described with minor modi cation (17). For wound healing assay, the cells were seeded in 60 mm cell culture dishes and allowed to achieved 90% con uence.…”

“…The quantitative real-time PCR was performed with SYBR qPCR Mix (Biosharp, Hefei, China) and analysis with a QuantStudio® 5 Real-Time PCR System (Applied Biosystems, Foster City, CA, USA) as previously described (17). The mRNA expression levels of PLAC8 were calculated using the 2 − DDCt method and normalized using the expression levels of glyceraldehyde 3-phosphate dehydrogenase (GAPDH).…”