Proteomic analysis reveals that Placenta-specific 9 induces cell proliferation and motility programs in human bronchial epithelial cells

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background: </jats:bold>Abnormal reprogramming of airway epithelium is a key cause of pulmonary diseases. The molecular mechanism underlying the abnormal reprogramming of airway epithelial cells (AECs) remains to be elucidated. Placenta-specific protein 9 (<jats:italic>Plac9</jats:italic>), a putative secretory protein, initially identified in placenta, has previously been shown to affect cell proliferation and motility in human embryonic hepatic cells. <jats:bold>Results: </jats:bold>Interestingly, we found that <jats:italic>Plac9</jats:italic> was repressed in lung cancers (LCs) compared to the corresponding normal tissues. We further investigated the role of <jats:italic>Plac9</jats:italic> in human bronchial epithelial cells by constructing a stable <jats:italic>Plac9</jats:italic>-overexpressing cell line (16HBE-GFP-<jats:italic>Plac9</jats:italic>) and analyzing the effect of <jats:italic>Plac9 </jats:italic>on cellular protein composition by using an isobaric tag for relative and absolute quantification (iTRAQ) proteomic approach. By gene ontology (GO) and pathway analyses, we found that GO terms and pathways associated with cell proliferation, cell cycle progression, and cell motility/migration were significantly enriched among the proteins regulated by <jats:italic>Plac9</jats:italic>. Consistently, we observed that overexpression of <jats:italic>Plac9</jats:italic> reduced cell proliferation and altered cell cycle progression. In addition, it also increased cell motility, including migration and invasion. <jats:bold>Conclusions: </jats:bold>Our findings suggest that <jats:italic>Plac9</jats:italic> inhibits cell proliferation through S phase arrest by altering cyclins/cyclin-dependent kinases (CDKs) and promotes cell motility likely via the concerted actions of cyclins, E-cadherin and vimentin, which may underlie <jats:italic>Plac9</jats:italic>-mediated abnormal human bronchial pathogenesis.</jats:p>