Mutual regulation of <scp>MDM</scp>4 and <scp>TOP</scp>2A in cancer cell proliferation

Liu, Tao; Zhang, Hailong; Yan, Sha; Gu, Liqun; Zhou, Mi

doi:10.1002/1878-0261.12457

Cited by 54 publications

(30 citation statements)

References 47 publications

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“…Conditioned medium of cancer cell lines was prepared as described previously (47). OS cell lines (MG63, U-2 OS, Saos-2, 143B, K2M2 and DLM8) were incubated in DMEM containing 10% FBS until the cells reached 80% confluence at 37°C.…”

Section: In Vitro Experimentsmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

et al. 2021

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Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells via receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP+ macrophages and C5_IFIT1+ macrophages were found to regulate regulatory T cells and participate in CD8+ T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8+ T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.

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Section: In Vitro Experimentsmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

et al. 2021

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“…TOP2A serves an important role in various biological behaviors of cells, including DNA replication, chromosome separation, chromatin concentration and gene expression ( 49 ). As a DNA replication- and cell division-regulating enzyme, TOP2A is the main target of several anticancer drugs, such as doxorubicin, etoposide, and mitoxantrone ( 50 ). High expression levels of TOP2A in various types of tumors, such as lung adenocarcinoma, bladder urothelial carcinoma, breast, prostate and colon cancer, indicates a poor prognosis ( 51 – 55 ), although this has not been previously reported in HCC.…”

Section: Discussionmentioning

confidence: 99%

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

et al. 2020

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Hepatocellular carcinoma (HCC) is a common malignant tumor in the clinic. Although there are increasing numbers of available treatment methods, their therapeutic effects are not satisfactory. The clinical indicators commonly used to predict the prognosis of HCC include tumor size, degree of cirrhosis, degree of tumor differentiation and tumor microvascular invasion; however, there are currently no molecular indicators that can predict the prognosis of HCC. Due to the differences in the progression of liver cancer among individuals, there is a growing need for prognostic biomarkers to accurately stratify patients for appropriate risk-adaptive treatment. The DNA topoisomerase 2-α (TOP2A) gene, which is located on human chromosome 17, encodes DNA topoisomerase IIα. Previous studies have demonstrated that TOP2A indicates a poor prognosis in patients with various types of tumors, but no such studies are currently available on HCC. By analyzing the differential expression of TOP2A in 50 pairs of tumor and paracancerous tissue samples in The Cancer Genome Atlas (TCGA) database, the present study revealed that the expression of TOP2A was significantly higher in tumor tissue compared with that in paracancerous tissue (P=6.319x10-16). In the collected clinical samples, the mRNA expression levels of TOP2A were significantly upregulated in HCC tumor tissues compared with those in the paracancerous tissues (P=6.40x10-3), suggesting that TOP2A was associated with the occurrence and development of liver cancer. In addition, the associations between TOP2A expression, clinicopathological features and prognosis were analyzed using a multi-center large sample dataset from TCGA database, and the results demonstrated that high expression of TOP2A was associated with a higher T stage, poorer clinical stage and higher histological grade compared with those in patients with low TOP2A expression. High expression of TOP2A was also identified to be associated with a poor prognosis of HCC, particularly in Asian populations. These results suggested that high expression of TOP2A in HCC tissues may be closely associated with tumor progression and metastasis, which may be used as a biological indicator to predict tumor prognosis in clinical practice.

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“…TOP2A is one of the nuclear matrix components. It has been found that overexpression of TOP2A is closely related to breast cancer, prostate cancer and liver cancer [19,20]. In normal tissues, PTTG1 is expressed in low amounts or not at all in normal tissue.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: A Bioinformatics-Based Screening and Analysis of Key Genes in Hepatocellular Carcinoma

Wei

Wang

Chen

et al. 2020

Preprint

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Hepatocellular carcinoma (HCC) is considered as the leading killer disease in the world. So far most of the diagnosis of HCC is mainly established on imaging and biopsy. As sequencing technology is developing quite fast, and it has already been widely applied in the medical area, such as cancer diagnosis. In this article, GSE121248, GSE76427 and GSE60502 datasets were chosen to analyze and screen key genes which could affect the development of liver cancer through the bioinformatics method. The results showed up regulated genes mainly reside in cell division, nucleus, protein binding pathway, and down regulated genes are mostly located in the Oxidation-reduction process, Extracellular region, Heme binding, Metabolic pathway. Secondly, hub gene analysis indicated there were twelve critical hub genes found: RFC4, RACGAP1, CCNB2, CDC20, UBE2C, PTTG1, AURKA, PRC1, NCAPG, CDKN3, TOP2A, KIF20A, AURKA and CDKN3. By applying bioinformatic measures , the genes associated with hepatocellular carcinoma can be efficiently analyzed, that would provide invaluable information for translational studies.

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Mutual regulation of MDM4 and TOP2A in cancer cell proliferation

Cited by 54 publications

References 47 publications

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

WITHDRAWN: A Bioinformatics-Based Screening and Analysis of Key Genes in Hepatocellular Carcinoma

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