Abstract
BackgroundProtein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown.MethodsQuantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues. We examined the clinical use of PRC1 in lung adenocarcinoma prognosis. Additionally, the tumorigenesis impact of PRC1 in lung adenocarcinoma cells was verified via in vitro and in vivo metastasis and tumorigenesis assays. Notably, Next Generation Sequencing (NGS) was performed to investigate the molecular mechanism underlying the oncogenic role of PRC1 in lung adenocarcinoma.ResultsPRC1 mRNA and protein expressions were upregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues. PRC1 protein overexpression correlated with lymph node metastasis and was an independent poor prognostic factor for lung adenocarcinoma patients. Our data implied that PRC1 depletion limited the proliferation and invasion of lung adenocarcinoma cells in vitro and lowered tumor development and lung metastasis in vivo. Remarkably, limiting PRC1 substantially prompted G2/M phase cell cycle arrest and apoptosis. Mechanistically, by conducting NGS on PRC1-depleted A549 cells and control cells, we discovered that PRC1 expression was significantly correlated with the Wnt signaling pathway.ConclusionsThis investigation offers confirmation that PRC1 is a prognostic and promising therapeutic biomarker for people with lung adenocarcinoma and takes on a key part in the activation of the Wnt/β-catenin pathway in lung adenocarcinoma development.
Highlights
Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis
In summary, we determined for the first time the expression pattern and molecular mechanism of PRC1 in lung adenocarcinoma
Our results provide a basis for the concept that overexpression of PRC1 in human lung adenocarcinoma may be important in the acquisition of an aggressive and poor prognostic phenotype
Summary
Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. Whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown. Lung cancer is the most frequently diagnosed cancer and the prominent reason for tumor-related death across the globe. 21.6% of all cancer-related deaths in China in 2015 were because of lung cancer [1]. NSCLC can be categorized into two typical subtypes: adenocarcinoma (AD) and squamous cell carcinoma (SCC). While treatment boosts patient prognosis, the 5-year survival rate of advanced lung cancer patients is just 10– 15% [3]. The poor prognosis of NSCLC is primarily because of the escalated rates of distant metastasis after resection. Determination of novel functional genes and biomarkers in tumor progression could offer different ways to treat patients with lung cancer
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