Comprehensive analysis of differentially expressed genes associated with PLK1 in bladder cancer

Zhang, Zhe; Zhang, Guojun; Gao, Zhipeng; Li, Shiguang; Li, Zeliang; Bi, Jianbin; Liu, Xiankui; Li, Zhenhua; Kong, Chuize

doi:10.1186/s12885-017-3884-2

Cited by 20 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While this study focused primarily on BORA, our transcriptomic data uncovered multiple pathways previously linked to activated-PLK1 functions. For instance, a gene expression microarray analysis of PLK1 knockdown in bladder cancer cells [50] revealed GO biological processes, such as cell cycle, focal adhesions, VEGF and NF-κB signaling pathways deregulated, similar to what we found in our transcriptomic analysis, hence underlying most of the pathways modulated by BORA are PLK1-dependent. Increasing evidence also supports that PLK1 has multiple nonmitotic functions in cancerous and noncancerous cells [51].…”

Section: Discussionsupporting

confidence: 82%

Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer

Parrilla

Barber

Majem

et al. 2020

Cancers

View full text Add to dashboard Cite

Identifying novel actionable factors that critically contribute to tumorigenesis is essential in ovarian cancer, an aggressive and disseminative tumor, with limited therapeutic options available. Here we show that Aurora Borealis (BORA), a mitotic protein that plays a key role in activating the master mitotic kinase polo-like kinase 1 (PLK1), has an oncogenic role in ovarian cancer. Gain and loss of function assays on mouse models and ex vivo patient-derived ascites cultures revealed an oncogenic role of BORA in tumor development and a transcriptome-analysis in clinically representative models depicted BORA's role in survival, dissemination and inflammatory cancer related-pathways. Importantly, combinatory treatments of FDA-approved inhibitors against oncogenic downstream effectors of BORA displayed synergistic effect in ovarian cancer models, offering promising therapeutic value. Altogether, our findings uncovered for the first time a critical role of BORA in the viability of human cancer cells providing potential novel therapeutic opportunities for ovarian cancer management.Cancers 2020, 12, 886 2 of 25 in cell cycle division. Nevertheless, even though BORA depletion has been reported to reduce the activity of PLK1 kinase, our understanding of its relevance in cancer is still very limited and there is no comprehensive study that defines the downstream biological consequences of BORA modulation in cancer. Recent evidence has shown that BORA is overexpressed in various tumors such breast, lung, and gastric adenocarcinomas and might serve as a prognostic biomarker [8].Ovarian cancer (OC), the most lethal gynecologic malignancy, is frequently diagnosed at advanced stages with disseminated disease, which limits the therapeutic options [9]. Despite improved cytoreductive surgical approaches and chemotherapy-based regimens, the survival of OC patients has remained largely unchanged during the last two decades [10,11]. Recent advances in cancer genomics have revealed that OC is molecularly a very heterogeneous disease, with extensive genomic instability, copy-number variations and defects in the homologous recombination repair pathway [12]. These genomic aberrations contribute to the development of tumor resistance, hampering effective treatment and ultimately causing disease recurrence [13], but also offer novel potential actionable vulnerabilities that can enhance the effectiveness of existing therapies.Molecular targeted therapies have been implemented routinely into the clinics changing OC management with the inclusion of anti-angiogenic compounds (i.e., monoclonal antibodies such Bevacizumab) [14,15] and poly ADP-ribose polymerases (PARP) inhibitors (i.e., Olaparib or Rucaparib) for breast-cancer (BRCA)-mutated carriers and BRCAness phenotype patients [16,17]. Synthetic lethality produced by PARP inhibitors enhances the therapeutic window after chemotherapy in recurrent platinum-sensitive OC subjects [18]. Nonetheless, it is effective in only a subset of patients, highlighting the urgent clinical need of searching...

show abstract

Section: Discussionsupporting

confidence: 82%

Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer

Parrilla

Barber

Majem

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…NDC80 is a downstream gene of polo-like kinase 1, which is a well-documented oncogene that serves a key role in cell reproduction and invasion (42). In bladder cancer, NDC80 was associated with the regulation of cell reproduction, migration and invasion, and was positively associated with metastasis (43). All of these results suggested that NDC80 serves an important role in the metastases of melanoma.…”

Section: Discussionmentioning

confidence: 99%

Identification of key candidate genes involved in melanoma metastasis

Chen

Shi

et al. 2019

Mol Med Report

View full text Add to dashboard Cite

Metastasis is the most lethal stage of cancer progression. The present study aimed to investigate the underlying molecular mechanisms of melanoma metastasis using bioinformatics. Using the microarray dataset GSE8401 from the Gene Expression Omnibus database, which included 52 biopsy specimens from patients with melanoma metastasis and 31 biopsy specimens from patients with primary melanoma, differentially expressed genes (DEGs) were identified, subsequent to data preprocessing with the affy package, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed. Mutated genes were analyzed with 80 mutated cases with melanoma from The Cancer Genome Atlas. The overall survival of key candidate DEGs, which were within a filtering of degree >30 criteria in the PPI network and involved three or more KEGG signaling pathways, and genes with a high mutation frequency were delineated. The expression analysis of key candidate DEGs, mutant genes and their associated genes were performed on UALCAN. Of the 1,187 DEGs obtained, 505 were upregulated and 682 were downregulated. ‘Extracellular exosome’ processes, the ‘amoebiasis’ pathway, the ‘ECM-receptor interaction’ pathway and the ‘focal adhesion’ signaling pathway were significantly enriched and identified as important processes or signaling pathways. The overall survival analysis of phosphoinositide-3-kinase regulator subunit 3 ( PIK3R3 ), centromere protein M ( CENPM ), aurora kinase A ( AURKA ), laminin subunit α 1 ( LAMA1 ), proliferating cell nuclear antigen ( PCNA ), adenylate cyclase 1 ( ADCY1 ), BUB1 mitotic checkpoint serine/threonine kinase ( BUB1 ), NDC80 kinetochore complex component ( NDC80 ) and protein kinase C α ( PRKCA ) in DEGs was statistically significant. Mutation gene analysis identified that BRCA1-associated protein 1 ( BAP1 ) had a higher mutation frequency and survival analysis, and its associated genes in the BAP1 -associated PPI network, including ASXL transcriptional regulator 1 ( ASXL1 ), proteasome 26S subunit, non-ATPase 3 ( PSMD3 ), proteasome 26S subunit, non ATPase 11 ( PSMD11 ) and ubiquitin C ( UBC ), were statistically significantly associated with the overall survival of patients with melanoma. The expression levels of PRKCA, BUB1, BAP1 and ASXL1 were significantly different between primary melanoma and metastatic melanoma. Based on the present study, ‘extracellular exosome’ processes, ‘amoebiasis’ pathways, ‘ECM-receptor interaction’ pathways and ‘focal adhesion’ signaling pathways may be important in the formation of metastases from melanoma. Th...

show abstract

“…In recent years, microarrays contingent on high-throughput platforms have emerged as a promising and efficient tool for screening significant genetic or epigenetic alternations in carcinogenesis and identifying promising biomarkers for diagnosis and prognosis of cancers [ 22 ]. Plentiful gene expression profiling microarrays have been employed to identify multifarious differentially expressed genes (DEGs) in various cancers, and a number of BC-related DEGs have therefore been documented [ 23 – 25 ]. Nonetheless, various additional critical genes and pathways associated with BC remain yet to be explored completely.…”

Section: Introductionmentioning

confidence: 99%

Melittin Constrains the Expression of Identified Key Genes Associated with Bladder Cancer

Jin

Yao

Xie

et al. 2018

Journal of Immunology Research

View full text Add to dashboard Cite

This work is aimed at investigating the effect of melittin on identified key genes in bladder cancer (BC) and further providing a theoretical basis for BC treatment. GSE35014 downloaded from the Gene Expression Omnibus (GEO) database was used to screen differentially expressed genes (DEGs) in BC cells and control. Results showed that a total of 389 upregulated and 169 downregulated genes were identified. Subsequently, GO analysis, KEGG pathway enrichment analysis, and PPI network analysis were employed to disclose the crucial genes and signaling pathways involved in BC. Fifteen module-related DEGs and their associated signaling pathways were obtained according to the PPI network and modular analyses. Based on the analysis of articles retrieved in the PubMed database, we found that melittin could induce apoptosis and constrain the progression of tumor cells as a result of regulating critical cancer-related signaling pathways, such as PI3K-Akt and TNF signaling pathways. Furthermore, PI3K-Akt and TNF signaling pathways were also found to be associated with module-related DEGs according to biological analyses. At last, qRT-PCR analysis demonstrated that melittin could constrain the expression of module-related DEGs (LPAR1, COL5A1, COL6A2, CXCL1, CXCL2, and CXCL3) associated with PI3K-Akt and TNF signaling pathways in BC cells. Functional assays revealed that melittin could constrain the proliferative and migrated abilities of BC cells. Conjointly, these findings provide a theoretical basis for these six genes as drug-sensitive markers of melittin in BC treatment.

show abstract

Comprehensive analysis of differentially expressed genes associated with PLK1 in bladder cancer

Cited by 20 publications

References 30 publications

Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer

Aurora Borealis (Bora), Which Promotes Plk1 Activation by Aurora A, Has an Oncogenic Role in Ovarian Cancer

Identification of key candidate genes involved in melanoma metastasis

Melittin Constrains the Expression of Identified Key Genes Associated with Bladder Cancer

Contact Info

Product

Resources

About