PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway.

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.

• Authors: Ping Zhan, Bin Zhang, Guang-Min Xi, Ying Wu, Hong-Bing Liu, Ya-Fang Liu, Wu-Jian Xu, Qing-Qing Zhu, Feng Cai, Ze-Jun Zhou, Ying-Ying Miu, Xiao-Xia Wang, Jia-Jia Jin, Qian Li, Li-Ping Qian, Tang-Feng Lv, Yong Song
• Journal: Molecular cancer (Mol Cancer) Vol. 16 Issue 1 Pg. 108 (06 24 2017) ISSN: 1476-4598 [Electronic] England
• PMID: 28646916 (Publication Type: Journal Article)

Chemical References

• CTNNB1 protein, human
• Cell Cycle Proteins
• PRC1 protein, human
• beta Catenin

Topics

• Adenocarcinoma (genetics, metabolism, mortality, pathology)
• Adenocarcinoma of Lung
• Aged
• Animals
• Apoptosis (genetics)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Female
• G2 Phase Cell Cycle Checkpoints (genetics)
• Gene Expression Regulation, Neoplastic
• High-Throughput Nucleotide Sequencing
• Humans
• Lung Neoplasms (genetics, metabolism, mortality, pathology)
• Male
• Mice, Inbred BALB C
• Middle Aged
• Prognosis
• Wnt Signaling Pathway (physiology)
• Xenograft Model Antitumor Assays
• beta Catenin (genetics, metabolism)