AURKA promotes cancer metastasis by regulating epithelial-mesenchymal transition and cancer stem cell properties in hepatocellular carcinoma

Chen, Chen-Lin; Song, Guangyuan; Xiang, Jue; Zhang, Hongcheng; Zhao, Shaoyun; Yu, Zhan

doi:10.1016/j.bbrc.2017.03.075

Cited by 99 publications

(102 citation statements)

References 25 publications

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“…AURKA protein kinase plays an important role in the development of malignant tumors. AURKA has been highly expressed in various malignant tumors, such as esophageal cancer, laryngeal cancer, liver cancer, and ovarian cancer [52][53][54]. AURKA may participate in the formation of tumors through two functions.…”

Section: Discussionmentioning

confidence: 99%

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Chu

Liu

et al. 2019

J Transl Med

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Background: Glioma accounts for a large proportion of cancer, and an effective treatment for this disease is still lacking because of the absence of specific driver molecules. Current challenges in the treatment of glioma are the accurate and timely diagnosis of brain glioma and targeted treatment plans. To investigate the diagnostic biomarkers and prospective role of miRNAs in the tumorigenesis and progression of glioma, we analyzed the expression of miRNAs and key genes in glioma based on The Cancer Genome Atlas database. Methods: Of the 701 cases that were downloaded, five were normal and 696 were glioma. Then, 1626 differentially expressed genes were identified, and 173 aberrantly expressed miRNAs were calculated by edgeR. GO and KEGG pathway enrichment analyses were performed using Cytoscape software. A coexpression network was built by weighted correlation network analysis (WGCNA). A cell scratch test and transwell, cell apoptosis and cell cycle assays were performed to validate the function of hsa-let-7b-5p. Results: Based on crosstalk genes in the KEGG, PPI network, and WGCNA analyses, PLK1, CCNA2, cyclin B2 (CCNB2), and AURKA were screened as candidate diagnostic marker genes. The survival analysis revealed that high mRNA expression of PLK1, CCNA2, and AURKA was significantly associated with poor overall survival. Furthermore, hsalet-7b-5p was identified as a core miRNA in the regulation of candidate genes involved in glioma development. We confirmed that hsa-let-7b-5p could inhibit the migration, invasion, and cell cycle of glioma cells. Conclusions: This study provides four potential biomarkers for the diagnosis of glioma, offers a potential explanation of its pathogenesis, and proposes hsa-let-7b-5p as a therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Chu

Liu

et al. 2019

J Transl Med

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“…The expression of MAP9 is downregulated in colorectal cancer, whereas AURKA and Plk1 are upregulated (Rouquier et al, 2014). Dysregulation of AURKA and Plk1 are strongly associated with tumorigenesis (Weng Ng et al, 2016;Al-Khafaji et al, 2017;Chen et al, 2017;Zhu et al, 2017), and AURKA polymorphisms have also been reported in association with GC and breast cancer (Lopez-Cortes et al, 2018;Mesic et al, 2017). Considering the direct interactions of MAP9 with AURKA and Plk1, we believe that MAP9 plays key role in carcinogenesis.…”

Section: Discussionmentioning

confidence: 85%

MAP9 single nucleotide polymorphism rs1058992 is a risk of EBV-associated gastric carcinoma in Chinese population

Liu¹,

Xiao²,

Wu³

et al. 2018

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Microtubule-associated protein 9 (MAP9) is a mitosis-associated protein involved in bipolar spindle assembly. Following DNA damage, MAP9 stabilizes p53 via p300 and MDM2 (mouse double minute-2 homolog). The dysregulation of MAP9 was considered to be associated with tumorigenesis. Single nucleotide polymorphisms (SNPs) in key genes governing mitosis may particularly increase susceptibility to gastric carcinoma (GC). Our study demonstrated that the CC homozygous genotype of SNP rs1058992 located in the MAP9 gene was significantly correlated with EBV-associated GC (EBVaGC) in a recessive genetic model (OR = 2.558, 95% CI = 1.306-5.010, P = 0.043), and the C allele frequency of rs1058992 also showed significant correlation with EBVaGC (OR = 1.904, 95% CI = 1.141-3.179, P = 0.013). These results suggest that the MAP9 rs1058992 polymorphism is associated with risk of EBVaGC. The conversion of lysine to arginine caused by rs1058992 may affect development of EBVaGC; however, further studies in larger populations are needed to fully elucidate its role in EBVaGC.

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“…PTEN and AURKA are aberrantly expressed in gastric cancer cells. AURKA has been reported to be involved in the formation of several types of gastrointestinal cancer (22)(23)(24)(25). However, the mechanism of interaction between AURKA and PTEN in gastric cancer has not been addressed.…”

Section: Resultsmentioning

confidence: 99%

Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA

Song

Liu

et al. 2018

Int J Mol Med

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Gastric adenocarcinoma remains a life‑threatening disease, emphasizing the importance of gaining an improved understanding of signaling pathways involved in this disease, which can lead to the development of novel therapeutic methods targeting common molecular pathways shared across different types of gastric adenocarcinoma. The present study revealed phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and aurora kinase A (AURKA) gene alterations, which were involved in changes in the phenotypes of gastric cancer cells, including increased proliferation by cell counting kit‑8 assay and invasion capacity by Transwell invasion assay, and predicted survival rates by KM Plotter database in gastric cancer. The present study investigated the association between PTEN and AURKA. Western blotting revealed that phosphorylated (p)-AURKA correlated with two target genes, PTEN and AURKA. The downregulation of PTEN by small interfering (si)RNA not only increased the expression of AURKA at the mRNA and protein levels by western blotting and by reverse transcription‑quantitative PCR, but also increased the expression of p‑AURKA by western blotting and immunofluorescence analysis. In addition, western blotting and reverse transcription‑quantitative PCR revealed that the downregulation of AURKA affected the expression level of PTEN. Furthermore, PTEN suppressed the malignant phenotypic changes of gastric adenocarcinoma cells by regulating the expression of AURKA inhibited by p‑AURKA, suggesting that p‑AURKA may be the key mediator of the PTEN‑associated activation of AURKA and may be key in maintaining the PTEN‑induced malignant state of gastric adenocarcinoma cells. This hypothesis was confirmed by western blotting, and changes were observed in the protein expression of p‑AURKA and AURKA under conditions in which cells were treated with either MLN8237 or si‑PTEN transfection only, or with si‑PTEN transfection and MLN8237. Knockdown of the expression of PTEN altered the expression of p‑AKT, p‑glycogen synthase kinase 3β and β‑catenin, which are genes that have been reported to be involved in the development of gastric adenocarcinoma. The present study confirmed that p‑AURKA is important in the development of gastric adenocarcinoma and revealed a novel functional link between PTEN, AURKA and p‑AURKA activation. The results also suggest a novel drug design strategy in targeting PTEN and AURKA for more specific gastric cancer cell death that spares normal cells.

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AURKA promotes cancer metastasis by regulating epithelial-mesenchymal transition and cancer stem cell properties in hepatocellular carcinoma

Cited by 99 publications

References 25 publications

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

Joint bioinformatics analysis of underlying potential functions of hsa-let-7b-5p and core genes in human glioma

MAP9 single nucleotide polymorphism rs1058992 is a risk of EBV-associated gastric carcinoma in Chinese population

Low expression of PTEN is essential for maintenance of a malignant state in human gastric adenocarcinoma via upregulation of p‑AURKA mediated by activation of AURKA

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