Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner

Wu, Fei; Lin, Yuanyuan; Cui, Peng; Liu, Hongyun; Zhang, Lechao; Sun, Zeqiang; Huang, Shiyuan; Li, Shun; Huang, Shiming; Zhao, Qing‐Li; Liu, Qingyong

doi:10.1007/s00280-018-3578-8

Cited by 23 publications

(19 citation statements)

References 19 publications

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“…Of note, knockdown of CDC20 caused inhibition of growth, migration ability and formation of colonies in lung cancer cells, as well as cell cycle arrest in G2/M phase and induction of apoptosis ( 39 ), making this oncogene a potential target molecule to address NSCLC therapy. Upregulation of CDC20 has been associated with shorter OS in patients with LUAD, but not in patients with LUSC ( 40 ), which is consistent with the results of the present study.…”

Section: Discussionsupporting

confidence: 92%

Identification of key differentially expressed mRNAs and microRNAs in non‑small cell lung cancer using bioinformatics analysis

Wang

Pan

2020

Exp Ther Med

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Non-small cell lung cancer (NSCLC) is a leading cause of mortality worldwide. However, the pathogenesis of NSCLC remains to be fully elucidated. Therefore, the present study aimed to explore the differential expression of mRNAs and microRNAs (miRNAs/miRs) in NSCLC and to determine how these RNA molecules interact with one another to affect disease progression. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified from the GSE18842, GSE32863 and GSE29250 datasets downloaded from the Gene Expression Omnibus (GEO database). Functional and pathway enrichment analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. STRING, Cytoscape and MCODE were applied to construct a protein-protein interaction (PPI) network and to screen hub genes. The interactions between miRNAs and mRNAs were predicted using miRWalk 3.0 and a miRNA-mRNA regulatory network was constructed. The prognostic value of the identified hub genes was then evaluated via Kaplan-Meier survival analyses using datasets from The Cancer Genome Atlas. A total of 782 DEGs and 46 DEMs were identified from the 3 GEO datasets. The enriched pathways and functions of the DEGs and target genes of the DEMs included osteoclast differentiation, cell adhesion, response to a drug, plasma membrane, extracellular exosome and protein binding. A subnetwork composed of 11 genes was extracted from the PPI network and the genes in this subnetwork were mainly involved in the cell cycle, cell division and DNA replication. A miRNA-gene regulatory network was constructed with 247 miRNA-gene pairs based on 6 DEMs and 210 DEGs. Kaplan-Meier survival analysis indicated that the expression of ubiquitin E2 ligase C, cell division cycle protein 20, DNA topoisomerase IIα, aurora kinase A and B, cyclin B2, maternal embryonic leucine zipper kinase, slit guidance ligand 3, phosphoglucomutase 5, endomucin, cysteine dioxygenase type 1, dihydropyrimidinase-like 2, miR-130b, miR-1181 and miR-127 was significantly associated with overall survival of patients with lung adenocarcinoma. In the present study, a miRNA-mRNA regulatory network in NSCLC was established, which may provide future avenues for scientific exploration and therapeutic targeting of NSCLC.

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Section: Discussionsupporting

confidence: 92%

Identification of key differentially expressed mRNAs and microRNAs in non‑small cell lung cancer using bioinformatics analysis

Wang

Pan

2020

Exp Ther Med

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“…2b , top panel). CDC20 is part of the anaphase-promoting complex APC(CDC20), and recent reports corroborate synergistic effects with DCT in PCa 18 , 19 . We confirmed the knockdown capacity of the siRNAs by western blotting (Fig.…”

Section: Resultsmentioning

confidence: 71%

A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor

et al. 2018

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Based on a molecular classification of prostate cancer using gene expression pathway signatures, we derived a set of 48 genes in critical pathways that significantly predicts clinical outcome in all tested patient cohorts. We tested these genes in a functional genomics screen in a panel of three prostate cancer cell lines (LNCaP, PC3, DU145), using RNA interference. The screen revealed several genes whose knockdown caused strong growth inhibition in all cell lines. Additionally, we tested the gene set in the presence of docetaxel to see whether any gene exhibited additive or synergistic effects with the drug. We observed a strong synergistic effect between DLGAP5 knockdown and docetaxel in the androgen-sensitive line LNCaP, but not in the two other androgen-independent lines. We then tested whether this effect was connected to androgen pathways and found that knockdown of the androgen receptor by si-RNA attenuated the synergy significantly. Similarly, androgen desensitized LNCaP-AI cells had a higher IC50 to docetaxel and did not exhibit the synergistic interaction. Short-term exposure to enzalutamide did not significantly alter the behaviour of parental LNCaP cells. An immunofluorescence analysis in LNCaP cells suggests that under the double insult of DLGAP5 knockdown and docetaxel, cells predominantly arrest in metaphase. In contrast, the knockdown of the androgen receptor by siRNA appears to assist cells to progress through metaphase in to anaphase, even in the presence of docetaxel. Our data suggest that DLGAP5 has a unique function in stabilizing spindle formation and surviving microtubule assault from docetaxel, in an androgen-regulated cell cycle system.

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“…The potential of CDC20 as a therapeutic target for human cancer treatment has been reported in previous studies (22). Wu et al (23) investigated the effects of CDC20 overexpression in docetaxel-and castration-resistant prostate cancer cell lines, and demonstrated that CDC20 mediated resistance in a Bim-dependent manner. Paul et al (24) indicated that CDC20 regulated the proteasome-mediated degradation of the tumor suppressor BTG3 associated nuclear protein, and inhibited apoptosis in breast cancer cells.…”

Section: Discussionmentioning

confidence: 84%

Identification of key genes associated with the progression of intrahepatic cholangiocarcinoma using weighted gene co‑expression network analysis

Zeng

et al. 2020

Oncol Lett

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The present study aimed to identify the key genes that are associated with the progression of intrahepatic cholangiocarcinoma through weighted gene co-expression network analysis (WGCNA). A total of three gene datasets were downloaded from the Gene Expression Omnibus database, including GSE107943, GSE119336 and GSE26566. Differentially expressed genes (DEGs) between intrahepatic cholangiocarcinoma tissues and adjacent liver tissues were identified using GSE107943, while tissue specific genes between bile duct and liver tissues were identified using GSE26566. Following the removal of tissue-specific genes, real DEGs were used to construct the WGCNA to investigate the association between gene modules and clinical traits. Following functional analysis, pathway enrichment analysis and the construction of a protein-protein interaction (PPI) network were performed, hub genes were selected and their diagnostic value was verified in GSE119336 using a receiver operating characteristic curve. Finally, the protein levels of the hub genes were also verified in intrahepatic cholangiocarcinoma tissues. A total of 1,643 real DEGs were identified and used to construct the WGCNA. Additionally, a total of seven co-expressed gene modules were identified following WGCNA, while genes in brown and yellow modules were identified to be associated with multiple clinical traits (the number of clinical traits >3) and used as key modules. A total of 63 core key module genes were subsequently identified, and it was indicated that these genes were most enriched in the nucleus (Gene Ontology term) and the cell cycle pathway (Kyoto Encyclopedia of Genes and Genomes term). Finally, a total of eight genes, including cyclin B1, cell division cycle 20, cell division cycle associated 8, cyclin dependent kinase 1, centrosomal protein 55, kinesin family member 2C, DNA topoisomerase IIα and TPX2 microtubule nucleation factor, exhibited the highest score in PPI analysis and had a high diagnostic value for intrahepatic cholangiocarcinoma. In addition, the protein levels of these genes were also revealed to be increased in most intrahepatic cholangiocarcinoma tissues. These eight genes may be used as novel biomarkers for the diagnosis of intrahepatic cholangiocarcinoma.

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Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner

Abstract: In conclusion, our data collectively demonstrated that Cdc20 overexpression facilitates the docetaxel resistant of the CRPC cell lines in a Bim-dependent manner. Furthermore, additionally targeting Cdc20 might be a promising solution for the treatment of the CRPC with docetaxel resistance.

Cited by 23 publications

References 19 publications

Identification of key differentially expressed mRNAs and microRNAs in non‑small cell lung cancer using bioinformatics analysis

Identification of key differentially expressed mRNAs and microRNAs in non‑small cell lung cancer using bioinformatics analysis

A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor

Identification of key genes associated with the progression of intrahepatic cholangiocarcinoma using weighted gene co‑expression network analysis

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