Background: Placenta-specific 9 (Plac9) is a putative secreted protein that was first discovered in the context of embryogenesis. The expression pattern of Plac9 during embryogenesis, together with the results of recent reports, suggest that Plac9 may play a role in the liver development. The present study was conducted to investigate the secretory characteristics of Plac9 and its potential role in liver cell physiology. Methods: Immunofluorescence was employed to identify the subcellular distribution of Plac9. Cellular proliferative activity was analyzed by MTT assay and cell colony formation. The cell cycle distribution of Plac9 was analyzed by flow cytometry, and a functional analysis was performed using L02 cells following their stable infection with a lentivirus over-expressing Plac9. Results: Plac9 is a novel protein that is localized to the cytoplasm and may be secreted through the classic endoplasmic reticulum-Golgi route. The overexpression of Plac9 inhibits cell growth and induces G2/M phase arrest. Conclusion: Our findings reveal a novel role for Plac9 in regulating cell growth.

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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.

Abstract Background: 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 (Plac9), a putative secretory protein, initially identified in placenta, has previously been shown to affect cell proliferation and motility in human embryonic hepatic cells. Results: Interestingly, we found that Plac9 was repressed in lung cancers (LCs) compared to the corresponding normal tissues. We further investigated the role of Plac9 in human bronchial epithelial cells by constructing a stable Plac9-overexpressing cell line (16HBE-GFP-Plac9) and analyzing the effect of Plac9 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 Plac9. Consistently, we observed that overexpression of Plac9 reduced cell proliferation and altered cell cycle progression. In addition, it also increased cell motility, including migration and invasion. Conclusions: Our findings suggest that Plac9 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 Plac9-mediated abnormal human bronchial pathogenesis.