Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis

Ma, Yue; Yang, Ju Hye; Wang, Ruozheng; Zhang, Zegao; Qi, Xiaoli; Liu, Chunhua; Ma, Miaomiao

doi:10.18632/oncotarget.15663

Cited by 13 publications

(11 citation statements)

References 52 publications

(57 reference statements)

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“…AURKA is associated with centrosomal expansion, spindle and chromosomal instability, and its high expression promotes tumor cell proliferation and invasion (Zhang, Wang, Liu, Hua, & Xin, 2009). The researchers (Sun et al, 2015) (Ma et al, 2017) found that AURKA is related to the resistance of taxol and radiosensitivity. Currently, AUARK inhibitors are being explored as molecular‐targeted medicines for the treatment of cervical cancer (Gabrielli et al, 2015; Umene et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Yang

Xue

et al. 2020

Molec Gen & Gen Med

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Background Cervical cancer as one of the most common malignant tumors lead to bad prognosis among women. Some researches already focus on the carcinogenesis and pathogenesis of cervical cancer, but it is still necessary to identify more key genes and pathways. Methods Differentially expressed genes were identified by GEO2R from the gene expression omnibus (GEO) website, then gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyzed by DAVID. Meanwhile, protein–protein interaction network was constructed by STRING, and both key genes and modules were found in visualizing network through Cytoscape. Besides, GEPIA did the differential expression of key genes and survival analysis. Finally, the expression of genes related to prognosis was further explored by UNLCAN, oncomine, and the human protein atlas. Results Totally 57 differentially expressed genes were founded, not only enriched in G1/S transition of mitotic cell cycle, mitotic nuclear division, and cell division but also participated in cytokine–cytokine receptor interaction, toll‐like receptor signaling pathway, and amoebiasis. Additionally, 12 hub genes and 3 key modules were screened in the Cytoscape visualization network. Further survival analysis showed that TYMS (OMIM accession number ), MCM2 (OMIM accession number ), HELLS (OMIM accession number ), TOP2A (OMIM accession number ), and CXCL8 (OMIM accession number ) were associated with the prognosis of cervical cancer. Conclusion This study aim to better understand the characteristics of some genes and signaling pathways about cervical cancer by bioinformatics, and could provide further research ideas to find new mechanism, more prognostic factors, and potential therapeutic targets for cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Yang

Xue

et al. 2020

Molec Gen & Gen Med

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“…Many researchers have found that four key genes were involved in cell cycle, participating in tumorigenesis and tumor proliferation. AURKA has been studied in a wide range of human malignancies and is associated with poor prognosis in several malignancies, including cervical squamous cell carcinoma, hepatocellular carcinoma, and nonsmall cell lung carcinoma (Ma et al, ; Wang et al, ; Zheng et al, ). Besides, Yang et al, () reported that AURKA as a transactivating co‐factor in the induction of the c‐Myc oncoprotein in breast cancer stem cells (BCSCs).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel biomarkers and small molecule drugs in human colorectal cancer by microarray and bioinformatics analysis

Chen¹,

Wang

Shen

et al. 2019

Molec Gen & Gen Med

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Background Colorectal cancer (CRC) is one of the most common malignant tumors. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma, and adenocarcinoma samples was downloaded to identify critical genes and potential drugs in CRC. Methods Expression profiles, GSE33113 and GSE44076, were integrated using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed by R language. Functional enrichment analyses of the DEGs were performed using the Database for Annotation, visualization, and integrated discovery (DAVID) database. Then, the search tool for the retrieval of interacting genes (STRING) database and Cytoscape were used to construct a protein–protein interaction (PPI) network and identify hub genes. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis (GEPIA). Connectivity Map (CMap) was used to query potential drugs for CRC. Results A total of 428 upregulated genes and 751 downregulated genes in CRC were identified. The functional changes of these DEGs were mainly associated with cell cycle, oocyte meiosis, DNA replication, p53 signaling pathway, and progesterone‐mediated oocyte maturation. A PPI network was identified by STRING with 482 nodes and 2,368 edges. Survival analysis revealed that high mRNA expression of AURKA, CCNB1, CCNF, and EXO1 was significantly associated with longer overall survival. Moreover, CMap predicted a panel of small molecules as possible adjuvant drugs to treat CRC. Conclusion Our study found key dysregulated genes involved in CRC and potential drugs to combat it, which may provide novel insights and potential biomarkers for prognosis, as well as providing new CRC treatments.

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“…Meanwhile, the correlation of tumor radioresistance with Aurora-A expression was also studied. Ma’ et al showed that Aurora-A affected radiosensitivity in cervical squamous cell carcinoma [31]. Venkataraman’ et al [32] showed that targeting Aurora Kinase A enhanced radiation sensitivity of atypical teratoid rhabdoid tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Aurora-a confers radioresistance in human hepatocellular carcinoma by activating NF-κB signaling pathway

et al. 2019

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BackgroundRadiotherapy failure is a significant clinical challenge due to the development of resistance in the course of treatment. Therefore, it is necessary to further study the radiation resistance mechanism of HCC. In our early study, we have showed that the expression of Aurora-A mRNA was upregulated in HCC tissue samples or cells, and Aurora-A promoted the malignant phenotype of HCC cells. However, the effect of Aurora-A on the development of HCC radioresistance is not well known.MethodsIn this study, colony formation assay, MTT assays, flow cytometry assays, RT-PCR assays, Western blot, and tumor xenografts experiments were used to identify Aurora-A promotes the radioresistance of HCC cells by decreasing IR-induced apoptosis in vitro and in vivo. Dual-luciferase reporter assay, MTT assays, flow cytometry assays, and Western blot assay were performed to show the interactions of Aurora-A and NF-κB.ResultsWe established radioresistance HCC cell lines (HepG2-R) and found that Aurora-A was significantly upregulated in those radioresistant HCC cells in comparison with their parental HCC cells. Knockdown of Aurora-A increased radiosensitivity of radioresistant HCC cells both in vivo and in vitro by enhancing irradiation-induced apoptosis, while upregulation of Aurora-A decreased radiosensitivity by reducing irradiation-induced apoptosis of parental cells. In addition, we have showed that Aurora-A could promote the expression of nuclear IkappaB-alpha (IκBα) protein while enhancing the activity of NF-kappaB (κB), thereby promoted expression of NF-κB pathway downstream effectors, including proteins (Mcl-1, Bcl-2, PARP, and caspase-3), all of which are associated with apoptosis.ConclusionsAurora-A reduces radiotherapy-induced apoptosis by activating NF-κB signaling, thereby contributing to HCC radioresistance. Our results provided the first evidence that Aurora-A was essential for radioresistance in HCC and targeting this molecular would be a potential strategy for radiosensitization in HCC.

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Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis

Cited by 13 publications

References 52 publications

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Identification of novel biomarkers and small molecule drugs in human colorectal cancer by microarray and bioinformatics analysis

Aurora-a confers radioresistance in human hepatocellular carcinoma by activating NF-κB signaling pathway

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