BACKGROUND: Aurora kinases (AURKs) family plays a vital role not only in cell division but also in tumorigenesis. However, there are still rare systematic analyses of the diverse expression patterns and prognostic value of the AURKs family in breast cancer (BC). Systematic bioinformatics analysis was conducted to explore the biological role, prognostic value, and immunologic function of AURKs family in BC. METHODS: The expression, prognostic value, and clinical functions of AURKs family in BC were evaluated with several bioinformatics web portals: ONCOMINE Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, Metascape, GeneMANIA, and LinkedOmics; and the result was verified using human tissues. RESULTS: The expression of AURKA and AURKB were upregulated in BC in subgroup analyses based on tumor stage (all P   <  0.05). BC patients with high AURKA and AURKB expression had a worse overall survival, relapse-free survival, and distant metastasis-free survival (all P   <  0.05). Verification experiment revealed that AURKA and AURKB were upregulated in BC ( P  < 0.05). AURKA and AURKB were specifically associated with several tumor-associated kinases (polo-like kinase 1 and cyclin-dependent kinase 1), miRNAs (miR-507 and miR-381), and E2F transcription factor 1. Moreover, AURKA and AURKB were correlated with immune cell infiltration. Functional enrichment analysis revealed that AURKA and AURKB were involved in the cell cycle signaling pathway, platinum drug resistance signaling pathway, ErbB signaling pathway, Hippo signaling pathway, and nucleotide-binding and oligomerization domain-like receptor signaling pathway. CONCLUSIONS Aurora kinases AURKA and AURKB could be employed as novel prognostic biomarkers or promising therapeutic targets for BC.
Humans ; Female ; Aurora Kinase A/metabolism* ; Aurora Kinase B/metabolism* ; Prognosis ; Breast Neoplasms/genetics* ; Neoplasm Recurrence, Local ; MicroRNAs

Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.
Animals ; Aurora Kinase B ; metabolism ; Aurora Kinase C ; metabolism ; Blastocyst ; metabolism ; Gene Expression Regulation, Developmental ; physiology ; Histones ; metabolism ; Mice ; Phosphorylation ; physiology

Aurora-B as an important kinase to adjust the cell normal mitosis is a potent target for cancer treatment. Aurora-B is overexpressed in a broad range of tumor and tumor cells are more sensitive while Aurora-B is inhibited. Due to the key role of the Aurora-B in cell mitosis, the development of its inhibitors is becoming more and more important. Several small molecules inhibit with a similar efficacy both Aurora-A and Aurora-B, however, in most cases the effects resemble Aurora-B disruption by genetic methods, indicating that Aurora-B represents an effective therapeutic target. There were several Aurora-B kinase inhibitors which had entered the clinics and displayed good antitumor activity. In this review, we will outline the functions of Aurora kinase B in normal cell division and in malignancy. We will focus on recent preclinical and clinical studies that have explored the mechanism of action and clinical effect of Aurora-B inhibitors in cancer treatment.
Animals ; Aurora Kinase B ; antagonists & inhibitors ; genetics ; metabolism ; Enzyme Activation ; Humans ; Mitosis ; Neoplasms ; drug therapy ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; RNA, Messenger ; metabolism

<b>OBJECTIVEb>To study the expression of Aurora-B in human glioma tissue and its significance.

<b>METHODSb>The total RNA was extracted from 41 human glioma tissues and 11 normal brain tissues by Trizol reagent. After reverse transcription of the total RNA into cDNAs, Aurora-B mRNA expressions in these samples were detected by quantitative real-time PCR. The protein expression in these samples was detected using immunohistochemical staining.

<b>RESULTSb>Aurora-B mRNA and protein expressions were significantly increased in glioma tissues as compared with those in normal brain tissues.

<b>CONCLUSIONb>Aurora-B mRNA and protein show markedly higher expressions in glioma tissue, suggesting that Aurora-B may be one of the malignant biomarkers in the pathogenesis and progression of human glioma.

Aurora Kinase B ; Aurora Kinases ; Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; enzymology ; pathology ; Female ; Glioma ; metabolism ; pathology ; Humans ; Male ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Tumor Cells, Cultured

<b>OBJECTIVEb>To study the expression of Aurora-B in non-small cell lung cancer (NSCLC) tissues and NSCLC cell lines.

<b>METHODb>Aurora-B expression was examined using immunohistochemical SP method in 91 stage I and 69 stage II-III NSCLC tissues and 40 adjacent tissues. The mRNA and protein expressions of Aurora-B in NSCLC cell lines (A549, H460 and H1299) were examined by RT-PCR and Western blotting, respectively.

<b>RESULTSb>The protein expression of Aurora-B was detected in 77.7% (94/121) of the tumor tissues and 9.8% (4/41) of the adjacent tissues, showing a significant difference between them (P<0.01). The positivity rate of Aurora-B protein was not related with the gender and age of NSCLC patients, but with lymph node metastasis, differentiation and histological type of NSCLC (P<0.05). Aurora-B was expressed in all the NSCLC cell lines (A549, H460 and H1299) at both mRNA and protein levels. A549 cells showed the highest expression of Aurora-B.

<b>CONCLUSIONb>Aurora-B protein is highly expressed in NSCLC tissues and cell lines, and may play a crucial role in the invasion, metastasis and development of NSCLC. The mRNA and protein expression levels of Aurora-B differ significantly between different NSCLC cell lines.

Adult ; Aged ; Aged, 80 and over ; Aurora Kinase B ; Aurora Kinases ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Tumor Cells, Cultured

<b>OBJECTIVEb>To detect the gene expression profile in gastric cancer cell cycle and explain the mechanism of gastric cancer cell proliferation by a genomic study.

<b>METHODSb>Gastric cancer cells MKN45 were synchronized at G2/M and G1/S point by nocodazole-thymidine and double thymidine methods. The synchronizing degree of cells was monitored by flow cytometry. The gene expression profiles at G2/M point, M/G1 transition, G1 early phase, G1 late phase, G1/S point, S early phase, S late phase, G2 early phase and G2 late phase in MKN45 cell cycling were examined using cDNA microarray chips. Hierarchy analysis was conducted with a professional software package and the up-regulated genes at G1 late and G2 phase were analyzed according to gene database. Furthermore, the mRNA level of cyclin E, cyclin B, plk1 and STK15 in above mentioned nine points were measured by quatitative PCR.

<b>RESULTSb>2001 genes were detected to be available at all 9 points via software processing, out of which 959 appeared up-regulated or down-regulated. 379 genes showed to be up-regulated at late G1 (147) or G2 phases (232), 40 at S and M phases (also up-regulated at G1 late and G2 phases). The 147 up-regulated genes at G1 late phase are involved in DNA metabolism, transcription and translation, protein transportation, ubiquitination and signal transduction, etc. The 232 up-regulated genes in G2 phase are involved in RNA synthesis and processing, intracellular protein transportation, cytoskeleton synthesis, signal transduction, apoptosis and anti-apoptosis, transcription regulation, ubiquitination, mitosis regulation and oncogene expression, etc. The mRNA level of 4 genes detected by quantitative PCR during cell cycle was in agreement with that detected by microarray.

<b>CONCLUSIONb>During MKN45 cell cycling, the preparation for DNA synthesis and chromosome separation are conducted in G1 and G2, which are implicated in multiple genes, may be the main impetus of driving MKN45 cell cycle. Some of these genes may be related to tumor over-proliferation. The cDNA microarray technique has characteristic features such as reliability and can provide a great deal for future research on cell cycle related genes in gastric cancer.

Aurora Kinase A ; Aurora Kinases ; Cell Cycle ; genetics ; Cell Cycle Proteins ; genetics ; Cell Line, Tumor ; Cyclin B ; genetics ; Cyclin E ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; methods ; Polymerase Chain Reaction ; methods ; Protein-Serine-Threonine Kinases ; genetics ; Proto-Oncogene Proteins ; genetics ; RNA, Messenger ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; pathology