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Published on: January 5, 2017
Comprehensive analysis of differentially expressed genes associated with PLK1 in bladder cancer
Zhe Zhang1,2, Guojun Zhang3, Zhipeng Gao1,2
1Department of Urology, First Hospital of China Medical University, 155 North Nanjing Street, Heping, Shenyang, Liaoning, 110001, China.
Background:
The significance of PLK1 (polo-like kinase 1) has become increasingly essential as both a biomarker and a target for cancer treatment. Here, we aimed to determine the downstream genes of PLK1 and their effects on the carcinogenesis and progression of bladder cancer.
Methods:
Specific siRNA was utilized to silence the target gene expression. The cell proliferation, invasion and migration of bladder cancer cells by MTT assay, BrdU assay and transwell assay. The differential expression genes were identified using Affymetrix HTA2.0 Array. The KEGG, GO and STRING analysis were used to analyze the signaling pathway and protein-protein interaction. Spearman analysis was used to analyze the correlation between protein and protein, between protein and clincopathologic characteristics.
Results:
PLK1 siRNA hindered the proliferation, invasion and migration of bladder cancer cells, as determined by the MTT, BrdU and transwell assays. A total of 561 differentially expressed genes were identified using an Affymetrix HTA2.0 Array in PLK1 knockdown T24 cells. According to KEGG, GO and STRING analysis, five key genes (BUB1B, CCNB1, CDC25A, FBXO5, NDC80) were determined to be involved in cell proliferation, invasion and migration. PLK1 knockdown decreased BUB1B, CCNB1, CDC25A and NDC80 expressions but increased FBXO5 expression. BUB1B, CCNB1, CDC25A and NDC80 were positively correlated with cell proliferation, invasion, migration and PLK1 expression in tissues, but FBXO5 was negatively correlated with each of those factors. The results showed that the five genes expressions were significantly correlation with the PLK1 expression in normal bladder tissues and bladder cancer tissues. Four of them (BUB1B, CCNB1, CDC25A, NDC80) were obviously positive correlations with pT stage and metastasis. But FBXO5 was negative correlated with pT stage and metastasis. Furthermore, significant correlations were found between CCNB1 or CDC25A or NDC80 and histological grade; between BUB1B or NDC80 and recurrence.
Conclusion:
Five downstream genes of PLK1 were associated with the regulation of cell proliferation, invasion and migration in bladder cancer. Furthermore, these genes may play important roles in bladder cancer and become important biomarkers and targets for cancer treatment.
Insights
Polo-like kinase 1 (PLK1) is crucial in bladder cancer. Its downstream genes, including BUB1B, CCNB1, CDC25A, FBXO5, and NDC80, significantly impact cancer progression and may serve as therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Polo-like kinase 1 (PLK1) is a key factor in cancer, acting as both a biomarker and therapeutic target.
- Understanding PLK1's downstream genes is vital for advancing bladder cancer treatment strategies.
Purpose of the Study:
- To identify downstream genes regulated by PLK1.
- To investigate the role of these genes in bladder cancer development and progression.
Main Methods:
- Gene silencing using siRNA to knockdown PLK1.
- Assays for cell proliferation (MTT, BrdU), invasion, and migration (Transwell).
- Gene expression profiling (Affymetrix HTA2.0 Array) and bioinformatic analyses (KEGG, GO, STRING, Spearman correlation).
Main Results:
- PLK1 inhibition reduced bladder cancer cell proliferation, invasion, and migration.
- 561 differentially expressed genes were identified upon PLK1 knockdown.
- Five key genes (BUB1B, CCNB1, CDC25A, FBXO5, NDC80) were linked to proliferation, invasion, and migration.
- BUB1B, CCNB1, CDC25A, and NDC80 expression correlated positively with cancer progression markers, while FBXO5 showed negative correlation.
Conclusions:
- PLK1 regulates bladder cancer cell proliferation, invasion, and migration through five key downstream genes.
- These identified genes represent potential biomarkers and therapeutic targets for bladder cancer treatment.
