The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer

An, Xin; Xu, Fei; Luo, Rongzhen; Zheng, Qiufan; Lu, Jiabin; Yang, Yanhua; Qin, Tao; Yuan, Zhongyu; Shi, Yanxia; Jiang, Wenqi; Wang, Shusen

doi:10.1186/s12885-018-4170-7

Cited by 62 publications

(53 citation statements)

References 38 publications

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“…EFNA3 is upregulated in Subtype-2, and previous studies show that it contributes to the metastatic spread of breast cancer [19]. Our model predicted that increased expression of LGR4, TESC, TOP2A, and ZNF695 is suggestive of increased invasive and metastatic activity in Subtype-2 [20]. Decreased expression of FGF10 is seen in Subtype-2 and predicted by our model is suggestive of dysplasia in LUAD subtype-2 samples [21].…”

Section: Resultssupporting

confidence: 53%

Prediction of best features in heterogeneous Lung adenocarcinoma samples using Least Absolute Shrinking and Selection Operator

Khaliq

Sharathchandra

Meenakshi

2019

Preprint

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4This study aims to create a tumor heterogeneity-based model for predicting the best features of 5 lung adenocarcinoma (LUAD) in multiple cancer subtypes using the Least Absolute Shrinking 6 and Selection Operator (LASSO). The RNA-Seq raw count data of 533 LUAD samples and 59 7 normal samples were downloaded from the TCGA data portal. Based on consensus clustering 8 method samples was divided into two subtypes, and clusters were validated using silhouette 9 width. Furthermore, we estimated subtypes for the abundance of immune and non-immune 1 6

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Section: Resultssupporting

confidence: 53%

Prediction of best features in heterogeneous Lung adenocarcinoma samples using Least Absolute Shrinking and Selection Operator

Khaliq

Sharathchandra

Meenakshi

2019

Preprint

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“…Topoisomerase-targeting anti-cancer drugs have been successfully used in the clinic, and their efficacy is based on topoisomerase poisoning (22). Recently, it has been reported that abnormal alterations and modifications of TOP2A may be critical to chromosome instability in some cancer types (23).…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed protein‑coding genes in lung adenocarcinomas

Wang

et al. 2019

Exp Ther Med

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Lung adenocarcinoma accounts for a high proportion of lung cancers. Though efforts have been made to develop new and effective treatments for this disease, the mortality rate remains high. Gene expression microarrays facilitate the study of lung cancer at the molecular level. The present study aimed to detect differentially expressed protein-coding genes to identify novel biomarkers and therapeutic targets for lung adenocarcinoma. Aberrations in gene expression in lung adenocarcinoma were determined by analysis of mRNA microarray datasets from the Gene Expression Omnibus database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks and statistical analysis were used to identify the biological functions of the differentially expressed genes (DEGs). The results of the bioinformatics analysis were subsequently validated using reverse transcription-quantitative PCR. A total of 303 DEGs were identified in lung adenocarcinomas, and they were enriched in a number of cancer-associated GO terms and KEGG pathways. DNA topoisomerase 2α (TOP2A), cell division cycle protein homolog 20 (CDC20), mitotic checkpoint serine/threonine protein kinase BUB1 (BUB1) and mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) exhibited the highest degree of interaction in the PPI network. Survival analysis performed using Kaplan-Meier curves and Cox regression indicated that these four genes were all significantly associated with the survival of patients with lung adenocarcinomas. In conclusion, TOP2A, CDC20, BUB1 and MAD2L1 may be key protein-coding genes that may serve as biomarkers and therapeutic targets in lung adenocarcinomas.

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“…The expression of abnormal topoisomerase plays a critical role in chromosome instability and tumorigenesis which has been shown to be a proliferation marker associated with the tumor grade [ 45 , 46 ]. Currently, the topo II-targeting drugs can be divided into two categories including poisons such as etoposide, mitoxantrone, and doxorubicin and catalytic inhibitors such merbarone and aclarubicin [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Heteronemin, a Marine Sesterterpenoid-Type Metabolite, Induces Apoptosis in Prostate LNcap Cells via Oxidative and ER Stress Combined with the Inhibition of Topoisomerase II and Hsp90

et al. 2018

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Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect. Accumulating evidence shows that heteronemin may act as a potent anticancer agent in clinical therapy. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in prostate cancer cells. Initially, heteronemin exhibited potent cytotoxic effect against LNcap and PC3 prostate cancer cells with IC50 1.4 and 2.7 μM after 24 h, respectively. In the xenograft animal model, the tumor size was significantly suppressed to about 51.9% in the heteronemin-treated group in comparison with the control group with no significant difference in the mice body weights. In addition, the results of a cell-free system assay indicated that heteronemin could act as topoisomerase II (topo II) catalytic inhibitor through the elimination of essential enzymatic activity of topoisomerase IIα expression. We found that the use of heteronemin-triggered apoptosis by 20.1–68.3%, caused disruption of mitochondrial membrane potential (MMP) by 66.9–99.1% and promoted calcium release by 1.8-, 2.0-, and 2.1-fold compared with the control group in a dose-dependent manner, as demonstrated by annexin-V/PI, rhodamine 123 and Fluo-3 staining assays, respectively. Moreover, our findings indicated that the pretreatment of LNcap cells with an inhibitor of protein tyrosine phosphatase (PTPi) diminished growth inhibition, oxidative and Endoplasmic Reticulum (ER) stress, as well as activation of Chop/Hsp70 induced by heteronemin, suggesting PTP activation plays a crucial rule in the cytotoxic activity of heteronemin. Using molecular docking analysis, heteronemin exhibited more binding affinity to the N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. Finally, heteronemin promoted autophagy and apoptosis through the inhibition of Hsp 90 and topo II as well as PTP activation in prostate cancer cells. Taken together, these multiple targets present heteronemin as an interesting candidate for its future development as an antiprostatic agent.

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The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer

Cited by 62 publications

References 38 publications

Prediction of best features in heterogeneous Lung adenocarcinoma samples using Least Absolute Shrinking and Selection Operator

Prediction of best features in heterogeneous Lung adenocarcinoma samples using Least Absolute Shrinking and Selection Operator

Identification of differentially expressed protein‑coding genes in lung adenocarcinomas

Heteronemin, a Marine Sesterterpenoid-Type Metabolite, Induces Apoptosis in Prostate LNcap Cells via Oxidative and ER Stress Combined with the Inhibition of Topoisomerase II and Hsp90

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