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

OBJECTIVE: To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR). METHODS: Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting. RESULTS: Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction. CONCLUSION Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.
Humans ; Aurora Kinase A/metabolism* ; Cell Line, Tumor ; Mitosis ; Cell Cycle ; Radiation, Ionizing ; RNA, Small Interfering/metabolism* ; Cyclin-Dependent Kinase Inhibitor p21/metabolism*

OBJECTIVETo study the expression of Aurora-B in human glioma tissue and its significance.

METHODSThe 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.

RESULTSAurora-B mRNA and protein expressions were significantly increased in glioma tissues as compared with those in normal brain tissues.

CONCLUSIONAurora-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

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

OBJECTIVETo investigate the role of STK15 gene amplification and overexpression to genesis and development of laryngeal squamous cell carcinoma (LSCC).

METHODSSTK15 gene amplification in 40 cases carcinoma tissues and normal tissues as control was detected by differential PCR approach. STK15 mRNA and protein levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry method.

RESULTSIn 40 LSCC cases, STK15 gene amplification was found in 14 tumor tissues(35%), mRNA overexpression in 27 tumor tissues(67.5%), and protein upregulated in 29 tumor tissues(72.5%). Statistics analysis showed that STK15 gene amplification and mRNA overexpression were obviously associated to differentiation degree of LSCC, and protein overexpression was closely associated with both differentiation degree and pathological grades of LSCC.

CONCLUSIONThis research results suggest that STK15 gene amplification contributes to its mRNA and protein overexpression through affecting the exact replication of centrosome and separation of chromosomes. STK15 gene thus plays a role in LSCC oncogenesis and malignant progression.

Aurora Kinase A ; Aurora Kinases ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Laryngeal Neoplasms ; genetics ; metabolism ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo explore the relationship between p53 gene mutations and STK15 abnormal expression in the development of human laryngeal squamous-cell carcinoma (LSCC).

METHODSLSCC tissues and matched normal tissues were taken during operation from 55 patients without previous chemotherapy or radiotherapy. Following polymerase chain reaction amplification direct sequencing single strand conformational polymorphism (PCR-SSCP) combined with silver staining were used to detect mutations of p53 gene in exons 7 and 8 (p53E7 and p53E8) using genomic DNA from 110 specimens including 55 LSCC tissues and 55 matched normal tissues. STK15 expression were evaluated by RT-PCR with beta-actin as internal control.

RESULTSThe mutation rate of p53E7 was 30.9% (compared to normal tissues, chi(2) = 8.66, P < 0.01). There was no mutation in p53E8. In 38 of the 55 cases (69.1%), the STK15 mRNA expression level was higher than that of the paired normal tissue. The STK15 to beta-actin ratio of average density value was 1.22 +/- 0.49 in the cancer tissue, and 0.99 +/- 0.54 in the normal tissues (t = 4.539, P < 0.01). In 14 of the 17 cases (82.4%) with p53E7 mutations, the STK15 expression was higher than that of normal tissue. In the 38 cases with STK15 over-expression, p53E7 mutation was found in 14 cases (36.8%). The rate of concurrence of p53E gene mutations and STK15 over-expression (25.5%) was higher than that of only p53E gene mutations (chi(2) = 26.025, P < 0.01).

CONCLUSIONThere is significant association between p53 gene mutation and STK15 over-expression in laryngeal squamous-cell carcinoma.

Actins ; metabolism ; Aurora Kinase A ; Aurora Kinases ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Exons ; Frameshift Mutation ; Gene Expression Regulation, Neoplastic ; Genes, p53 ; genetics ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; Mutation, Missense ; Protein-Serine-Threonine Kinases ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics

OBJECTIVEThe aim of this study was to investigate the prognostic value of combined expression of Aurora A, Ki-67, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer (NSCLC).

METHODSExpressions of Aurora A, Ki-67, p53 and p21 WAF1 in 58 tumor samples from resected primary NSCLCs were detected by immunohistochemistry. The correlation of proteins, survival and clinicopathological characteristics was analyzed.

RESULTSThe positive rates of Aurora A, Ki-67, p53 and p21 WAF1 expression were 89.7% (52/58), 53.4% (31/58), 46.6% (27/58) and 34.5% (20/58), respectively. Aurora A expression was positively correlated with nodal metastasis (69.2% vs. 37.8%, P = 0.045). The univariable analysis showed that the overall survival (OS) was 75.0%in patients with low Aurora A expression and 46.0% in patients with high Aurora A expression (P = 0.039). The 3-year survival rate was 40.0% in patients with positive expression of Aurora A and p53, 65.0% in the patients with positive expression of Aurora A or p53, and 82.1% in the patients with negative expression of Aurora A and p53 (P = 0.039). The Cox regression model showed that combined expression of Aurora and p53 is an independent factor affecting the prognosis of NSCLC patients (P = 0.015).

CONCLUSIONSOur findings suggest that the positive expression of Aurora A, Ki-67 and p53 proteins is an unfavorable factor affecting the prognosis for NSCLC patients, and the overexpression of Aurora A is an independent unfavorable factor association with shorter OS in NSCLC patients. Detection of positive Aurora A and p53 expression may be a useful predictive prognostic indicator for NSCLC patients.

Aurora Kinase A ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; surgery ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; surgery ; Prognosis ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo investigate the effects of knockdown of Aurora-A by RNA interference on laryngeal cancer Hep-2 cell growth in vitro and in vivo.

METHODSA plasmid containing siRNA against Aurora-A was constructed and transfected into human laryngeal cancer cell line Hep-2. Measurements included the CCK-8 assay for viability and proliferation, Transwell assay for invasion, colony formation assay for cell anchorage-independent growth. Western blot and immunohistochemistry assay for protein expression. Tumorigenicity was observed in vivo.

RESULTSIn Hep-2 cells transfected by Aurora-A siRNA (designated as siRNA-3), protein expression of Aurora-A was suppressed by 52%. In CCK-8 assay, absorbance value of siRNA-3 cells (3.268 ± 0.106, (x(-) ± s)) was lower than that of Hep-2 cells (3.722 ± 0.152, F = 17.634, P < 0.001). In Transwell assay, the average invasive cells per field in siRNA-3 cells (110.0 ± 18.0) was less than that in Hep-2 cells (236.0 ± 26.0, F = 26.462, P < 0.01). In colony formation assay, the average colony number of siRNA-3 cells (31.0 ± 6.6) was lower than that of Hep-2 cells (104.0 ± 14.0). The average tumor size in siRNA-3 group was (127.77 ± 174.83) mm(3), which was less than Hep-2 cell group (837.26 ± 101.80) mm(3), (F = 28.187, P < 0.001). Silencing of Aurora-A decreased the expression of focal adhesion kinase (FAK) and matrix metalloproteinase-2 (MMP-2), key regulators in cell adhesion and invasion.

CONCLUSIONSThe knockdown of Aurora-A inhibits the growth and invasiveness of Hep-2 cells in vitro and in vivo, which may be a promising therapeutic strategy for LSCC.

Animals ; Aurora Kinase A ; Aurora Kinases ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Gene Silencing ; Humans ; Laryngeal Neoplasms ; genetics ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Mice ; Mice, Nude ; Protein-Serine-Threonine Kinases ; genetics ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection

OBJECTIVETo study the expression of Aurora-B in non-small cell lung cancer (NSCLC) tissues and NSCLC cell lines.

METHODAurora-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.

RESULTSThe 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.

CONCLUSIONAurora-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