The Identification of Key Gene Expression Signature and Biological Pathways in Metastatic Renal Cell Carcinoma

Bao, Lin; Zhao, Ye; Liu, Chenchen; Cao, Qi; Huang, Yu; Chen, Ke; Song, Zhengshuai

doi:10.7150/jca.38379

Cited by 5 publications

(3 citation statements)

References 63 publications

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“…In breast cancer, the level of AURKB is overexpressed and related to low survival rate of patient. In rental cancer, the expression of AURKB associated with clinical and pathological characteristics of patients with rental cancer and its expression levels were independent prognostic factors for rental cancer 57 , 58 . These evidences suggested that AURKB could be not only a potential target but also be a proliferation-independent prognostic factor.…”

Section: Discussionmentioning

confidence: 98%

HI-511 overcomes melanoma drug resistance via targeting AURKB and BRAF V600E

Chang¹,

Zhang²,

Wang³

et al. 2020

Theranostics

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Rationale: Melanoma is an aggressive tumor of the skin and drug resistance is still a major problem in melanoma therapy. Novel targets and effective agents to overcome drug resistant melanoma are urgently needed in clinical therapy. Methods: Gene Expression Omnibus (GEO) database analysis, pathway enrichment analysis, and survival rate analysis were utilized to identify a candidate target. An anchorage-independent cell growth assay, flow cytometry, Western blot, and a xenograft mouse model were used to study the function of Aurora kinase B (AURKB) in both drug-sensitive and drug-resistant melanoma. Next, HI-511, a novel dual-target inhibitor targeting both AURKB and BRAF V600E, was designed and examined by an in vitro kinase assay. Methods as indicated above in addition to a BRAF V600E/PTEN-loss melanoma mouse model were used to demonstrate the effect of HI-511 on melanoma development in vitro and in vivo . Results: AURKB is highly expressed in melanoma and especially in vemurafenib-resistant melanoma and the expression was correlated with patient survival rate. Knocking down AURKB inhibited cell growth and induced apoptosis in melanoma, which was associated with the BRAF/MEK/ERKs and PI3-K/AKT signaling pathways. Importantly, we found that HI-511, a novel dual-target inhibitor against AURKB and BRAF V600E, suppresses both vemurafenib-sensitive and vemurafenib-resistant melanoma growth in vitro and in vivo by inducing apoptosis and mediating the inhibition of the BRAF/MEK/ERKs and PI3K/AKT signaling pathways. Conclusion: AURKB is a potential target for melanoma treatment. HI-511, a novel dual-target inhibitor against both AURKB and BRAF V600E, could achieve durable suppression of melanoma growth, even drug-resistant melanoma growth.

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Section: Discussionmentioning

confidence: 98%

HI-511 overcomes melanoma drug resistance via targeting AURKB and BRAF V600E

Chang¹,

Zhang²,

Wang³

et al. 2020

Theranostics

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“… 19 Previous studies have reported that high AURKB expression indicated worse prognosis, and the expression of AURKB expression tended to rise with enhancing T stage and G grade of tumor. 20 AURKB is one of nine genes that related to poor survival of ccRCC analyzed by The Cancer Genome Atlas and Total Cancer Care data. 21 Bioinformatics analysis suggests that AURKB and KIF18B are closely related in ccRCC tissues, and when both of them are active they can accelerate the progression of ccRCC and indicate poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Label-free quantitative proteomics reveals the mechanisms of Aurora kinase B in renal cell carcinoma

Li,

Yang

2024

SAGE Open Medicine

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Background: Renal cell carcinoma is the most common form of kidney cancer which is a global threat to human health, needing to explore effective therapeutic targets and treatment methods. Aurora kinase B acts as an important carcinogenic role in various kinds of tumors, while its mechanism in renal cell carcinoma is indistinct. Herein we explore the underlying mechanism of Aurora kinase B in renal cell carcinoma. Methods and results: Label-free quantitative proteomics analysis was employed to analyze the differentially expressed proteins in 786-O cells which were treated with si-Aurora kinase B or si-ctrl. In the current study, 169 differentially expressed proteins were identified. The top 10 upregulated proteins were MX2, IFI44L, ISG20, DDX58, F3, IFI44, ECE1, PRIC285, NIT1, and IFIT2. The top 10 downregulated proteins were FKBP9, FSTL1, DDAH1, TGFB2, HMGN3, COIL, FAM65A, PTPN14, ARFGAP2, and EIF2C2. GO enrichment analysis showed that these differentially expressed proteins participated in biological processes, including defense response to virus, response to virus, and type I interferon signaling pathway. These differentially expressed proteins participated in cellular components, including focal adhesion, cell-substrate adherens junction, cell-substrate junction, and endoplasmic reticulum lumen. These differentially expressed proteins participated in molecule functions, including guanyl nucleotide binding, nucleotidase activity, double-stranded RNA binding, 2′-5′-oligoadenylate synthetase activity, and virus receptor activity. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the significantly changed proteins including OAS3, OAS2, JAK1, TAP1, and RAC1 were involved in Epstein-Barr virus infection. Conclusions: Taken together, our results demonstrate the possible mechanisms that Aurora kinase B may participate in renal cell carcinoma. These findings may provide insights into tumorigenesis and a theoretical basis for developing potential therapies of renal cell carcinoma.

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“…Among the seven genes, AURKB and PTTG1 have been reported to act as oncogenes (perezdecastro 2006) during spindle formation or chromosome segregation. Lin Bao et al showed that AURKB was overexpressed in ccRCC while AURKB knockdown significantly inhibited the migration and invasion of ACHN cells (Bao et al, 2020). Atsushi Okato et al documented that dual strands of pre-miR-149 act as antitumor miRNAs by targeting FOXM1 in ccRCC cells (Okato et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Prognostic Gene Signature in Clear Cell Renal Cell Carcinoma

Zhan

Wang

et al. 2021

Front. Mol. Biosci.

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Clear cell renal cell carcinoma (ccRCC), one of the most common urologic cancer types, has a relatively good prognosis. However, clinical diagnoses are mostly done during the medium or late stages, when mortality and recurrence rates are quite high. Therefore, it is important to perform real-time information tracking and dynamic prognosis analysis for these patients. We downloaded the RNA-seq data and corresponding clinical information of ccRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 3,238 differentially expressed genes were identified between normal and ccRCC tissues. Through a series of Weighted Gene Co-expression Network, overall survival, immunohistochemical and the least absolute shrinkage selection operator (LASSO) analyses, seven prognosis-associated genes (AURKB, FOXM1, PTTG1, TOP2A, TACC3, CCNA2, and MELK) were screened. Their risk score signature was then constructed. Survival analysis showed that high-risk scores exhibited significantly worse overall survival outcomes than low-risk patients. Accuracy of this prognostic signature was confirmed by the receiver operating characteristic curve and was further validated using another cohort. Gene set enrichment analysis showed that some cancer-associated phenotypes were significantly prevalent in the high-risk group. Overall, these findings prove that this risk model can potentially improve individualized diagnostic and therapeutic strategies.

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The Identification of Key Gene Expression Signature and Biological Pathways in Metastatic Renal Cell Carcinoma

Cited by 5 publications

References 63 publications

HI-511 overcomes melanoma drug resistance via targeting AURKB and BRAF V600E

HI-511 overcomes melanoma drug resistance via targeting AURKB and BRAF V600E

Label-free quantitative proteomics reveals the mechanisms of Aurora kinase B in renal cell carcinoma

Development and Validation of a Prognostic Gene Signature in Clear Cell Renal Cell Carcinoma

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