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Published in: Targeted Oncology 6/2016

01-12-2016 | Original Research Article

Effect of AURKA Gene Expression Knockdown on Angiogenesis and Tumorigenesis of Human Ovarian Cancer Cell Lines

Published in: Targeted Oncology | Issue 6/2016

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Abstract

Background

Ovarian cancer is one of the most common malignant gynecological cancers. Higher expression of AURKA has been found in immortalized human ovarian epithelial cells in previous studies, implying the relationship between AURKA and ovarian cancer pathogenesis.

Aim

We investigated the effect of AURKA on angiogenesis and tumorigenesis of human ovarian cancer cells.

Methods

Firstly, the expression of AURKA in HO8910 and SKOV3 ovarian cancer cell lines was knocked down using a vector expressing a short hairpin small interfering RNA (shRNA). Next, the effect of knockdown of AURKA on cell angiogenesis, proliferation, migration, and invasion was determined by microtubule formation assay, proliferation assay, transwell migration, and invasion assays. In addition, the effect of AURKA knockdown on angiogenesis and tumorigenesis was also determined in a chicken chorioallantoic membrane (CAM) model and in nude mice.

Results

The results of the microtubule formation assay indicated that knockdown of AURKA significantly inhibited ovarian cancer cell-induced angiogenesis of endothelial cells compared to its control (P < 0.001). Knockdown of AURKA also significantly inhibited cell proliferation, migration, and invasion of HO8910 and SKOV3 cells in vitro. Furthermore, the Matrigel plug assay showed that knockdown of AURKA significantly repressed ovarian cancer cell-induced angiogenesis in nude mice (P < 0.05), and the CAMs model also showed that AURKA knockdown significantly attenuated the angiogenesis (P < 0.001) and tumorigenesis (P < 0.001) of HO8910 cells compared to the control. Finally, the tumorigenicity assay in vivo further indicated that AURKA shRNA reduced tumorigenesis in nude mice inoculated with ovarian cancer cells (P < 0.001).

Conclusions

These results suggest the potential role of AURKA in angiogenesis and tumorigenesis of ovarian cancer, which may provide a potential therapeutic target for the disease.
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Literature
2.
go back to reference Tan DS, Agarwal R, Kaye SB. Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol. 2006;7(11):925–34.CrossRefPubMed Tan DS, Agarwal R, Kaye SB. Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol. 2006;7(11):925–34.CrossRefPubMed
3.
4.
go back to reference Abiko K et al. PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction. Clin Cancer Res. 2013;19(6):1363–74.CrossRefPubMed Abiko K et al. PD-L1 on tumor cells is induced in ascites and promotes peritoneal dissemination of ovarian cancer through CTL dysfunction. Clin Cancer Res. 2013;19(6):1363–74.CrossRefPubMed
5.
go back to reference Akutagawa N et al. Expression of vascular endothelial growth factor and E-cadherin in human ovarian cancer: association with ascites fluid accumulation and peritoneal dissemination in mouse ascites model. Jpn J Cancer Res. 2002;93(6):644–51.CrossRefPubMed Akutagawa N et al. Expression of vascular endothelial growth factor and E-cadherin in human ovarian cancer: association with ascites fluid accumulation and peritoneal dissemination in mouse ascites model. Jpn J Cancer Res. 2002;93(6):644–51.CrossRefPubMed
6.
go back to reference Fu J et al. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res. 2007;5(1):1–10.CrossRefPubMed Fu J et al. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res. 2007;5(1):1–10.CrossRefPubMed
7.
8.
go back to reference Wang X et al. Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene. 2006;25(54):7148–58.CrossRefPubMed Wang X et al. Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene. 2006;25(54):7148–58.CrossRefPubMed
9.
10.
go back to reference Zhou H et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet. 1998;20(2):189–93.CrossRefPubMed Zhou H et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet. 1998;20(2):189–93.CrossRefPubMed
11.
go back to reference Zhang Z et al. Activation of BTAK expression in primary ovarian surface epithelial cells of prophylactic ovaries. Mod Pathol. 2007;20(10):1078–84.CrossRefPubMed Zhang Z et al. Activation of BTAK expression in primary ovarian surface epithelial cells of prophylactic ovaries. Mod Pathol. 2007;20(10):1078–84.CrossRefPubMed
12.
go back to reference Do TV et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene. 2014;33(5):539–49.CrossRefPubMed Do TV et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene. 2014;33(5):539–49.CrossRefPubMed
13.
go back to reference Jeng YM et al. Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res. 2004;10(6):2065–71.CrossRefPubMed Jeng YM et al. Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res. 2004;10(6):2065–71.CrossRefPubMed
14.
go back to reference Kamada K et al. Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep. 2004;12(3):593–9.PubMed Kamada K et al. Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. Oncol Rep. 2004;12(3):593–9.PubMed
15.
go back to reference Tatsuka M et al. Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis. Oncogene. 2005;24(6):1122–7.CrossRefPubMed Tatsuka M et al. Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis. Oncogene. 2005;24(6):1122–7.CrossRefPubMed
16.
go back to reference Rojanala S et al. The mitotic serine threonine kinase, Aurora-2, is a potential target for drug development in human pancreatic cancer. Mol Cancer Ther. 2004;3(4):451–7.PubMed Rojanala S et al. The mitotic serine threonine kinase, Aurora-2, is a potential target for drug development in human pancreatic cancer. Mol Cancer Ther. 2004;3(4):451–7.PubMed
17.
go back to reference Yakushijin Y, Hamada M, Yasukawa M. The expression of the aurora-A gene and its significance with tumorgenesis in non-Hodgkin’s lymphoma. Leuk Lymphoma. 2004;45(9):1741–6.CrossRefPubMed Yakushijin Y, Hamada M, Yasukawa M. The expression of the aurora-A gene and its significance with tumorgenesis in non-Hodgkin’s lymphoma. Leuk Lymphoma. 2004;45(9):1741–6.CrossRefPubMed
18.
go back to reference Macarulla T, Ramos FJ, Tabernero J. Aurora kinase family: a new target for anticancer drug. Recent Pat Anticancer Drug Discov. 2008;3(2):114–22.CrossRefPubMed Macarulla T, Ramos FJ, Tabernero J. Aurora kinase family: a new target for anticancer drug. Recent Pat Anticancer Drug Discov. 2008;3(2):114–22.CrossRefPubMed
19.
go back to reference Ren J et al. Tumor markers for early detection of ovarian cancer. Expert Rev Mol Diagn. 2010;10(6):787–98.CrossRefPubMed Ren J et al. Tumor markers for early detection of ovarian cancer. Expert Rev Mol Diagn. 2010;10(6):787–98.CrossRefPubMed
20.
go back to reference Dominguez-Brauer C et al. Targeting mitosis in cancer: emerging strategies. Mol Cell. 2015;60(4):524–36.CrossRefPubMed Dominguez-Brauer C et al. Targeting mitosis in cancer: emerging strategies. Mol Cell. 2015;60(4):524–36.CrossRefPubMed
21.
go back to reference Hamada M et al. Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-Hodgkin’s lymphoma. Br J Haematol. 2003;121(3):439–47.CrossRefPubMed Hamada M et al. Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-Hodgkin’s lymphoma. Br J Haematol. 2003;121(3):439–47.CrossRefPubMed
22.
go back to reference Qin D et al. Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi’s sarcoma-associated herpesvirus by herpes simplex virus type 1. BMC Microbiol. 2011;11:240.CrossRefPubMedPubMedCentral Qin D et al. Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi’s sarcoma-associated herpesvirus by herpes simplex virus type 1. BMC Microbiol. 2011;11:240.CrossRefPubMedPubMedCentral
23.
go back to reference Aranda E, Owen GI. A semi-quantitative assay to screen for angiogenic compounds and compounds with angiogenic potential using the EA.hy926 endothelial cell line. Biol Res. 2009;42(3):377–89.CrossRefPubMed Aranda E, Owen GI. A semi-quantitative assay to screen for angiogenic compounds and compounds with angiogenic potential using the EA.hy926 endothelial cell line. Biol Res. 2009;42(3):377–89.CrossRefPubMed
25.
go back to reference Bobbin ML, Rossi JJ. RNA interference (RNAi)-based therapeutics: delivering on the promise? Annu Rev Pharmacol Toxicol. 2016;56:103–22.CrossRefPubMed Bobbin ML, Rossi JJ. RNA interference (RNAi)-based therapeutics: delivering on the promise? Annu Rev Pharmacol Toxicol. 2016;56:103–22.CrossRefPubMed
26.
go back to reference Mendiola M et al. Aurora kinases as prognostic biomarkers in ovarian carcinoma. Hum Pathol. 2009;40(5):631–8.CrossRefPubMed Mendiola M et al. Aurora kinases as prognostic biomarkers in ovarian carcinoma. Hum Pathol. 2009;40(5):631–8.CrossRefPubMed
27.
go back to reference Gritsko TM et al. Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res. 2003;9(4):1420–6.PubMed Gritsko TM et al. Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res. 2003;9(4):1420–6.PubMed
28.
go back to reference Moreno-Bueno G et al. Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res. 2003;63(18):5697–702.PubMed Moreno-Bueno G et al. Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res. 2003;63(18):5697–702.PubMed
29.
go back to reference Tanner MM et al. Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res. 2000;6(5):1833–9.PubMed Tanner MM et al. Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res. 2000;6(5):1833–9.PubMed
30.
go back to reference Ye Q, Lei L, Aili AX. Identification of potential targets for ovarian cancer treatment by systematic bioinformatics analysis. Eur J Gynaecol Oncol. 2015;36(3):283–9.PubMed Ye Q, Lei L, Aili AX. Identification of potential targets for ovarian cancer treatment by systematic bioinformatics analysis. Eur J Gynaecol Oncol. 2015;36(3):283–9.PubMed
Metadata
Title
Effect of AURKA Gene Expression Knockdown on Angiogenesis and Tumorigenesis of Human Ovarian Cancer Cell Lines
Publication date
01-12-2016
Published in
Targeted Oncology / Issue 6/2016
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-016-0436-7

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