Article ; Online: PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway.
Molecular cancer
2017 Volume 16, Issue 1, Page(s) 108
Abstract: ... on a key part in the activation of the Wnt/β-catenin pathway in lung adenocarcinoma development. ... However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown.: Methods: Quantitative ... the tumorigenesis impact of PRC1 in lung adenocarcinoma cells was verified via in vitro and in vivo metastasis and ...
| Abstract | Background: 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. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown. Methods: Quantitative 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. Results: PRC1 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. Conclusions: This 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. |
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| MeSH term(s) | Adenocarcinoma/genetics ; Adenocarcinoma/metabolism ; Adenocarcinoma/mortality ; Adenocarcinoma/pathology ; Adenocarcinoma of Lung ; Aged ; Animals ; Apoptosis/genetics ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Female ; G2 Phase Cell Cycle Checkpoints/genetics ; Gene Expression Regulation, Neoplastic ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Mice, Inbred BALB C ; Middle Aged ; Prognosis ; Wnt Signaling Pathway/physiology ; Xenograft Model Antitumor Assays ; beta Catenin/genetics ; beta Catenin/metabolism |
| Chemical Substances | CTNNB1 protein, human ; Cell Cycle Proteins ; PRC1 protein, human ; beta Catenin |
| Language | English |
| Publishing date | 2017-06-24 |
| Publishing country | England |
| Document type | Journal Article |
| ISSN | 1476-4598 |
| ISSN (online) | 1476-4598 |
| DOI | 10.1186/s12943-017-0682-z |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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