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Chinese Journal of Thoracic Surgery(Electronic Edition) ›› 2023, Vol. 10 ›› Issue (03): 164-175. doi: 10.3877/cma.j.issn.2095-8773.2023.03.06

• Original Article • Previous Articles     Next Articles

Effects of protein regulator of cytokinesis 1 on migration, invasion and proliferation of lung adenocarcinoma cell

Shihao Li, Zihao Li, Bo Dong, Chunli Wu, Bin Wu, Yinliang Sheng, Yu Qi()   

  1. Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • Received:2022-10-06 Revised:2023-01-30 Accepted:2023-05-16 Online:2023-08-28 Published:2023-10-17
  • Contact: Yu Qi

Abstract:

Objective

To investigate the effect of protein regulator of cytokinesis 1 (PRC1) on lymph node metastasis, migration, proliferation and prognosis of lung adenocarcinoma.

Methods

The non-small cell lung cancer expression matrix was obtained from Gene Expression Omnibus (GEO), including GSE7670, GSE32863 and GSE68465. Firstly, differential analysis was performed on the three datasets to obtain differentially expressed genes, which were then subjected to enrichment analysis. Secondly, the clinical and expression data of differentially expressed genes were obtained from The Cancer Genome Atlas (TCGA) database. The data was used for weighted gene co-expression network analysis (WGCNA) to obtain the module most relevant to clinical characteristics including tumor stage and lymph node metastasis. Thirdly, the hub gene was obtained through analysis of the module genes using the Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) and binary logistic regression analysis. Subsequently, the expression level of PRC1 in both mRNA and protein levels between lung adenocarcinoma and normal tissues was validated. After knocking down the expression of PRC1 in human lung adenocarcinoma cell line H1299, in vitro functional experiments were conducted to validate the impact of PRC1 on the proliferation, migration, and invasion abilities of lung adenocarcinoma cells. T-test was used to compare the difference of PRC1 expression between normal and tumor tissues, and binary logistic regression analysis was performed to identify independent factors affecting tumor prognosis. Additionally, the downstream mechanism of PRC1 in regulating the metastasis of lung adenocarcinoma cells was investigated.

Results

The expression level of PRC1 was higher in lung adenocarcinoma tissues compared to normal lung tissues, at both mRNA and protein levels, with statistical significance. The cells in the Si-PRC1 group were significantly lower than that in the control group in migration experiments (P<0.001), invasion experiments (P<0.001), and scratch experiments (P<0.001). The proliferation ability of Si-PRC1 group cells was significantly lower than that of the control group at 72 and 96 hours. Patients with high expression of PRC1 in lung adenocarcinoma had shorter overall survival (P=0.0014). The qPCR results showed that E-cadherin expression was significantly upregulated (P<0.001) in PRC1 knockdown cells, while N-cadherin and Vimentin expression were significantly downregulated (P<0.01). Western blot results showed that the activated phosphorylated MAPK signal was weakened in PRC1 knockout tumor cells.

Conclusions

PRC1 is associated with poor prognosis of LUAD patients and affects lymph node metastasis and tumor cells proliferation, migration and invasion. PRC1 is a potential therapeutic target for lung adenocarcinoma.

Key words: Lung adenocarcinoma, Protein regulator of cytokinesis 1, Weighted gene co-expression network analysis, Prognosis

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