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AURKB Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT.

ABSTRACT: Aim:To investigate the function of Aurora kinase B (AURKB) in gastric cancer (GC). Methods:Immunohistochemistry was used to assay the expression of AURKB in 50 pairs of GC and adjacent tissues, and qRT-PCR was conducted to test AURKB expression in normal gastric epithelial and GC cell lines. Two segments of small interference RNAs (siRNAs) targeting AURKB were synthesized and inserted into GV248 lentivirus vector. After transfected with LV-AURKB-RNAis, CCK8, wound healing, transwell and flow cytometric assays were performed to determine the influence of silencing AURKB on cell proliferation, invasion, migration, cell cycles and apoptosis of GC cells, and the expression of EMT (epithelial-mesenchymal transition)-related markers was demonstrated by Western blots (WB). Results:AURKB was highly expressed in GC and closely associated with lymph node metastasis and advanced stages of GC. Down-regulating AURKB suppressed the proliferation and promoted the apoptosis of GC cells, arrested the cell cycle in G2/M phase, and inhibited the invasion and migration of GC cells. The expression levels of AKT1, mTOR, Myc, MMP2, and VEGFA were decreased, while the expression levels of OCLN and JUP were increased after knocking down of AURKB in both AGC and MKN45 cells. Conclusion:AURKB is overexpressed in GC and closely associated with clinicopathologic characteristics of GC. It is likely that by inhibiting VEGFA/Akt/mTOR and Wnt/?-catenin/Myc pathways, silenced AURKB could inhibit the invasive and migratory abilities of GC cells. However, because of the small sample size and the absence of in-vivo experiments, these results should be verified by further studies.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7415439 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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<i>AURKB</i> Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT.

Wang Zhen Z Yu Zhu Z Wang Gong-He GH Zhou Yi-Ming YM Deng Jian-Ping JP Feng Yue Y Chen Jun-Qiang JQ Tian Lei L

Cancer management and research 20200805

<h4>Aim</h4>To investigate the function of Aurora kinase B (AURKB) in gastric cancer (GC).<h4>Methods</h4>Immunohistochemistry was used to assay the expression of AURKB in 50 pairs of GC and adjacent tissues, and qRT-PCR was conducted to test <i>AURKB</i> expression in normal gastric epithelial and GC cell lines. Two segments of small interference RNAs (siRNAs) targeting <i>AURKB</i> were synthesized and inserted into GV248 lentivirus vector. After transfected with LV-AURKB-RNAis, CCK8, wound he ...[more]

PMID: 32801915

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Project description:BackgroundTumour-derived exosomes have recently been shown to participate in the formation and progression of different cancer processes, including tumour microenvironment remodelling, angiogenesis, invasion, metastasis, and drug resistance. However, the function and mechanism of exosome-encapsulated nucleic acids and proteins in bladder cancer remain unclear. This study aimed to investigate the effects of tumour-derived exosomes on the tumorigenesis and development of bladder cancer.MethodsIn this study, gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database and two independent Gene Expression Omnibus (GEO) datasets. The nucleic acids and proteins encapsulated in bladder cancer-derived exosomes were obtained from the ExoCarta database. Based on these databases, the expression patterns of exosomal mRNAs and proteins and the matched clinicopathological characteristics were analysed. Furthermore, we carried out a series of experiments to verify the relevant findings.ResultsA total of 7280 differentially expressed mRNAs were found in TCGA data, of which 52 mRNAs were shown to be encapsulated in bladder cancer-derived exosomes. Survival analysis based on the UALCAN database showed that among the top 10 upregulated and the top 10 downregulated exosomal genes, only the expression of KRT6B had a statistically significant effect on the survival of bladder cancer patients. Additionally, clinical correlation analysis showed that the elevated level of KRT6B was highly associated with bladder cancer stage, grade, and metastasis status. GSEA revealed that KRT6B was involved not only in epithelial-mesenchymal transition-related pathways but also in the immune response in bladder cancer. Ultimately, our experimental results were also consistent with the bioinformatic analysis.ConclusionKRT6B, which can be detected in bladder cancer-derived exosomes, plays an important role in the epithelial-mesenchymal transition and immune responses in bladder cancer. Further research will enable its potentially prognostic marker and therapeutic target for bladder cancer.

Dataset Information

AURKB Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT.

Publications

<i>AURKB</i> Promotes the Metastasis of Gastric Cancer, Possibly by Inducing EMT.

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