Silencing of Aurora kinase A by RNA interference inhibits tumor growth in human osteosarcoma cells by inducing apoptosis and G2/M cell cycle arrest

Jiang, Zhenhuan; Jiang, Jiannong; Yang, Huilin; Zhang, Ge; Wang, Qiang; Zhang, Leiyan; Wu, Chenguang; Wang, Jinzhi

doi:10.3892/or.2014.2986

Cited by 16 publications

(12 citation statements)

References 18 publications

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“…CENPA phosphorylation requires the enrichment of AURKB to maintain the phosphorylation on Ser7 at inner centromeres and for kinetochore function [ 26 – 28 ]. Jiang et al [ 29 ] showed that silencing of AURKA expression in osteosarcoma cells significantly decreased both colony formation ability in vitro and tumorigenesis ability in vivo as well as induced cell apoptosis and G2/M cell cycle arrest in osteosarcoma cells. In addition, the median survival time was significantly longer in patients with low- CENPA expression osteosarcomas than in those with high- CENPA expression osteosarcomas.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines

et al. 2015

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BackgroundThis study aimed to better understand the mechanisms underlying methotrexate (MTX)—resistance in osteosarcoma.MethodsThe raw transcription microarray data GSE16089 collected from three MTX-sensitive osteosarcoma (Saos-2) cell samples and three MTX-resistant osteosarcoma (Saos-2) cell samples were downloaded from Gene Expression Omnibus. After data processing, the differentially expressed genes (DEGs) were identified. Next, DEGs were submitted to DAVID for functional annotation based on the GO (Gene Ontology) database, as well as pathway enrichment analysis based on the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. Transcription factors (TFs) and tumor-associated genes (TAGs) were identified with reference to TRANSFAC and TAG, and TSGene databases, respectively. The protein-protein interaction (PPI) network of the gene-encoded products was constructed, and the subnetwork with the highest score was also detected using Search Tool for the Retrieval of Interacting Genes and BioNet package.ResultsA total of 690 up-regulated genes and down-regulated 626 genes were identified. Up-regulated DEGs (including AARS and PARS2) were associated to transfer RNA (tRNA) aminoacylation while down-regulated DEGs (including AURKA, CCNB1, CCNE2, CDK1, and CENPA) were correlated with mitotic cell cycle. Totally, 13 TFs (including HMGB2), 13 oncogenes (including CCNA2 and AURKA), and 19 tumor suppressor genes (TSGs) (including CDKN2C) were identified from the down-regulated DEGs. Ten DEGs, including nine down-regulated genes (such as AURKA, CDK1, CCNE2, and CENPA) and one up-regulated gene (GADD45A), were involved in the highest score subnetwork.ConclusionAARS, AURKA, AURKB, CENPA, CCNB1, CCNE2, and CDK may contribute to MTX resistance via aminoacyl-tRNA biosynthesis pathway, cell cycle pathway, or p53 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines

et al. 2015

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“…Aurora kinase A and B are overexpressed in various sarcomas, including chondrosarcoma, osteosarcoma, synovial sarcoma, and Ewing sarcoma, and are associated with poor prognosis and metastasis 104–107 . Targeting aurora kinase A and B with small molecule kinase inhibitors, shRNA, and siRNA exhibited inhibition of tumor cells 105, 107 . Moreover, a study demonstrated that the combination of aurora kinase A and B kinase inhibitor VX-680 (Tozasertib) with etoposide and doxorubicin showed synergistic effects in Ewing sarcoma 107 .…”

Section: Targeting Serine/threonine Protein Kinases To Reverse Mdr Inmentioning

confidence: 99%

Targeting protein kinases to reverse multidrug resistance in sarcoma

Chen

Shen

Choy

et al. 2016

Cancer Treatment Reviews

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Sarcomas are a group of cancers that arise from transformed cells of mesenchymal origin. They can be classified into over 50 subtypes, accounting for approximately 1% of adult and 15% of pediatric cancers. Wide surgical resection, radiotherapy, and chemotherapy are the most common treatments for the majority of sarcomas. Among these therapies, chemotherapy can palliate symptoms and prolong life for some sarcoma patients. However, sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multidrug resistance (MDR). MDR attenuates the efficacy of anticancer drugs and results in treatment failure for sarcomas. Therefore, overcoming MDR is an unmet need for sarcoma therapy. Certain protein kinases demonstrate aberrant expression and/or activity in sarcoma cells, which have been found to be involved in the regulation of sarcoma cell progression, such as cell cycle, apoptosis, and survival. Inhibiting these protein kinases may not only decrease the proliferation and growth of sarcoma cells, but also reverse their resistance to chemotherapeutic drugs to subsequently reduce the doses of anticancer drugs and decrease drug side-effects. The discovery of novel strategies targeting protein kinases opens a door to a new area of sarcoma research and provides insight into the mechanisms of MDR in chemotherapy. This review will focus on the recent studies in targeting protein kinase to reverse chemotherapeutic drug resistance in sarcoma.

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“…The solution may thus not lie in targeting DNA, but rather in identifying other relevant cellular targets in osteosarcoma cells. Current investigation in the field suggests the Wnt signalling pathway (Guo et al 2007), the aurora kinase A (AURKA) (Jiang et al 2014), and the Rhoassociated coil containing protein kinase 1 (ROCK1) (Liu et al 2011) as promising new targets for the inhibition of osteosarcoma growth and/or progression.…”

Section: Discussionmentioning

confidence: 99%

Supramolecular adducts of native and permethylated β-cyclodextrins with (2,2′-dipyridylamine)chlorido(1,4,7-trithiacyclononane)ruthenium(II) chloride: solid-state and biological activity studies

et al. 2017

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The complex [([9]aneS 3 )Ru II (dipa)Cl]Cl (1, where dipa = 2,2 0 -dipyridylamine) was included into native b-cyclodextrin (b-CD) and permethylated b-CD (TRIMEB) by co-dissolution followed by solvent removal. Two adducts were obtained with a 1:1 host:guest stoichiometry. Solid-state studies of the guest comprised collecting the single-crystal structure of its 3.5 hydrate form and also powder diffraction on the remaining bulk material, showing it is isotypical with the harvested crystal for X-ray analysis. Solid-state studies of the cyclodextrin adducts were carried out by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), 13 C{ 1 H} CP/MAS NMR and FTIR spectroscopies. Biological studies on 1 and its adducts comprised the evaluation of the shift caused by 1 on the melting temperature of DNA (DT m ), as well as the evaluation of cytotoxicity by the MTT assay on the osteosarcoma MG-63 cell line. 1414MG-63 cell line. m, 1356MG-63 cell line. m, 1337MG-63 cell line. m, 1299MG-63 cell line. m, 1273MG-63 cell line. w, 1261MG-63 cell line. w, 1240MG-63 cell line. m, 1159 s, 1123 m, 1080 s, 1027 vs, 1000 s, 947 m, 935 m, 910 w, 848 m, 827 w, 775 m, 763 m, 709 m, 609 m, 576 m, 532 m, 440 w, 420 w, 402 w, 369 vw, 355 vw, 335 vw, 329 vw, 324 vw, 303 w, 289 w.

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Silencing of Aurora kinase A by RNA interference inhibits tumor growth in human osteosarcoma cells by inducing apoptosis and G2/M cell cycle arrest

Cited by 16 publications

References 18 publications

Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines

Identification of genes associated with methotrexate resistance in methotrexate-resistant osteosarcoma cell lines

Targeting protein kinases to reverse multidrug resistance in sarcoma

Supramolecular adducts of native and permethylated β-cyclodextrins with (2,2′-dipyridylamine)chlorido(1,4,7-trithiacyclononane)ruthenium(II) chloride: solid-state and biological activity studies

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