Analysis of microarray-identified genes and microRNAs associated with drug resistance in ovarian cancer

被引:2
作者
Zou, Jing [1 ]
Yin, Fuqiang [2 ]
Wang, Qi [1 ]
Zhang, Wei [1 ]
Li, Li [1 ]
机构
[1] Guangxi Med Univ, Affiliated Tumor Hosp, Dept Gynecol Oncol, Nanning 530021, Guangxi, Peoples R China
[2] Guangxi Med Univ, Med Sci Res Ctr, Nanning 530021, Guangxi, Peoples R China
关键词
Ovarian cancer; drug resistance; expression profiling microarray; gene; microRNA; bioinformatics; CISPLATIN SENSITIVITY; MULTIDRUG-RESISTANCE; DNA METHYLATION; CELLS; EXPRESSION; CARCINOMA; PLATINUM; MECHANISM; PATHWAYS; GENOMICS;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of this study was to identify potential microRNAs and genes associated with drug resistance in ovarian cancer through web-available microarrays. The drug resistant-related microRNA microarray dataset GS54665 and mRNA dataset GSE33482, GSE28646, and GSE15372 were downloaded from the Gene Expression Omnibus database. Dysregulated microRNAs/genes were screened with GEO2R and were further identified in SKOV3 (SKOV3/DDP) and A2780 (A2780/DDP) cells by real-time quantitative PCR (qRT-PCR), and then their associations with drug resistance was analyzed by comprehensive bioinformatic analyses. Nine microRNAs (microRNA-199a-5p, microRNA-199a-3p, microRNA-199b-3p, microRNA-215, microRNA-335, microRNA-18b, microRNA-363, microRNA-645 and microRNA-141) and 38 genes were identified to be differentially expressed in drug-resistant ovarian cancer cells, with seven genes (NHSL1, EPHA3, USP51, ZSCAN4, EPHA7, SNCA and PI15) exhibited exactly the same expression trends in all three microarrays. Biological process annotation and pathway enrichment analysis of the 9 microRNAs and 38 genes identified several drug resistant-related signaling pathways, and the microRNA-mRNA interaction revealed the existence of a targeted regulatory relationship between the 9 microRNAs and most of the 38 genes. The expression of 9 microRNAs and the 7 genes by qRT-PCR in SKOV3/DDP and A2780/DDP cells indicating a consistent expression profile with the microarrays. Among those, the expression of EPHA7 and PI15 were negatively correlated with that of microRNA-141, and they were also identified as potential targets of this microRNA via microRNA-mRNA interaction. We thus concluded that microRNA-141, EPHA7, and PI15 might jointly participate in the regulation of drug resistance in ovarian cancer and serve as potential targets in targeted therapies.
引用
收藏
页码:6847 / U2783
页数:14
相关论文
共 45 条
[1]   P73 regulates cisplatin-induced apoptosis in ovarian cancer cells via a calcium/calpain-dependent mechanism [J].
Al-Bahlani, S. ;
Fraser, M. ;
Wong, A. Y. C. ;
Sayan, B. S. ;
Bergeron, R. ;
Melino, G. ;
Tsang, B. K. .
ONCOGENE, 2011, 30 (41) :4219-4230
[2]   GLI1 upregulates C-JUN through a specific 130-kDa isoform [J].
Amable, Lauren ;
Gavin, Elaine ;
Kudo, Kenji ;
Meng, Erhong ;
Rocconi, Rodney P. ;
Shevde, Lalita A. ;
Reed, Eddie .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2014, 44 (03) :655-661
[3]   ENHANCEMENT OF MELPHALAN TOXICITY BY OCTANOL IN OVARIAN ADENOCARCINOMA CELL-LINES - EFFECTS OF ALTERED CELL-CELL COMMUNICATION, GLUTATHIONE LEVELS, AND PLASMA-MEMBRANE FLUIDITY [J].
BARHOUMI, R ;
BAILEY, RH ;
HUTCHINSON, RW ;
BOWEN, JA ;
BURGHARDT, RC .
FUNDAMENTAL AND APPLIED TOXICOLOGY, 1995, 25 (01) :70-79
[4]   NCBI GEO: archive for functional genomics data sets-update [J].
Barrett, Tanya ;
Wilhite, Stephen E. ;
Ledoux, Pierre ;
Evangelista, Carlos ;
Kim, Irene F. ;
Tomashevsky, Maxim ;
Marshall, Kimberly A. ;
Phillippy, Katherine H. ;
Sherman, Patti M. ;
Holko, Michelle ;
Yefanov, Andrey ;
Lee, Hyeseung ;
Zhang, Naigong ;
Robertson, Cynthia L. ;
Serova, Nadezhda ;
Davis, Sean ;
Soboleva, Alexandra .
NUCLEIC ACIDS RESEARCH, 2013, 41 (D1) :D991-D995
[5]   TP53 oncomorphic mutations predict resistance to platinum- and taxane-based standard chemotherapy in patients diagnosed with advanced serous ovarian carcinoma [J].
Brachova, Pavla ;
Mueting, Samuel R. ;
Carlson, Matthew J. ;
Goodheart, Michael J. ;
Button, Anna M. ;
Mott, Sarah L. ;
Dai, Donghai ;
Thiel, Kristina W. ;
Devor, Eric J. ;
Leslie, Kimberly K. .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2015, 46 (02) :607-618
[6]   Characterization of LY2228820 Dimesylate, a Potent and Selective Inhibitor of p38 MAPK with Antitumor Activity [J].
Campbell, Robert M. ;
Anderson, Bryan D. ;
Brooks, Nathan A. ;
Brooks, Harold B. ;
Chan, Edward M. ;
De Dios, Alfonso ;
Gilmour, Raymond ;
Graff, Jeremy R. ;
Jambrina, Enrique ;
Mader, Mary ;
McCann, Denis ;
Na, Songqing ;
Parsons, Stephen H. ;
Pratt, Susan E. ;
Shih, Chuan ;
Stancato, Louis F. ;
Starling, James J. ;
Tate, Courtney ;
Velasco, Juan A. ;
Wang, Yong ;
Ye, Xiang S. .
MOLECULAR CANCER THERAPEUTICS, 2014, 13 (02) :364-374
[7]   The PI3K/Akt/mTOR pathway in ovarian cancer: therapeutic opportunities and challenges [J].
Cheaib, Bianca ;
Auguste, Aurelie ;
Leary, Alexandra .
CHINESE JOURNAL OF CANCER, 2015, 34 (01) :4-16
[8]   ToppGene Suite for gene list enrichment analysis and candidate gene prioritization [J].
Chen, Jing ;
Bardes, Eric E. ;
Aronow, Bruce J. ;
Jegga, Anil G. .
NUCLEIC ACIDS RESEARCH, 2009, 37 :W305-W311
[9]   Tissue factor expression in ovarian cancer: implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor [J].
Cocco, Emiliano ;
Varughese, Joyce ;
Buza, Natalia ;
Bellone, Stefania ;
Lin, Ken-Yu ;
Bellone, Marta ;
Todeschini, Paola ;
Silasi, Dan-Arin ;
Azodi, Masoud ;
Schwartz, Peter E. ;
Rutherford, Thomas J. ;
Carrara, Luisa ;
Tassi, Renata ;
Pecorelli, Sergio ;
Lockwood, Charles J. ;
Santin, Alessandro D. .
CLINICAL & EXPERIMENTAL METASTASIS, 2011, 28 (07) :689-700
[10]   Clonal Architectures and Driver Mutations in Metastatic Melanomas [J].
Ding, Li ;
Kim, Minjung ;
Kanchi, Krishna L. ;
Dees, Nathan D. ;
Lu, Charles ;
Griffith, Malachi ;
Fenstermacher, David ;
Sung, Hyeran ;
Miller, Christopher A. ;
Goetz, Brian ;
Wendl, Michael C. ;
Griffith, Obi ;
Cornelius, Lynn A. ;
Linette, Gerald P. ;
McMichael, Joshua F. ;
Sondak, Vernon K. ;
Fields, Ryan C. ;
Ley, Timothy J. ;
Mule, James J. ;
Wilson, Richard K. ;
Weber, Jeffrey S. .
PLOS ONE, 2014, 9 (11)