Chemoresistance in ovarian cancer linked to expression of microRNAs

被引:33
作者
Frederick, P. J. [1 ]
Green, H. N. [2 ]
Huang, J. S. [3 ]
Egger, M. E. [3 ]
Frieboes, H. B. [3 ]
Grizzle, W. E. [2 ]
McNally, L. R. [3 ]
机构
[1] Roswell Pk Canc Inst, Buffalo, NY 14263 USA
[2] Univ Alabama Birmingham, Birmingham, AL USA
[3] Univ Louisville, Louisville, KY 40202 USA
关键词
chemotherapy resistance; epithelial ovarian cancer; microRNA; UP-REGULATION; PROFILES; MIR-21; RESISTANCE; CARCINOMA; ANTIBODY; THERAPY; MARKERS; TRA-8;
D O I
10.3109/10520295.2013.788736
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
We evaluated the differential expression of several microRNAs (miRNAs) among malignant cells in ascites and matched omental metastasis in patients with epithelial ovarian cancer (EOC). Ascites and omental tumors were collected prospectively from five patients who were undergoing primary surgical cytoreduction. Patient samples were processed and treated with carboplatin, paclitaxel and combination chemotherapy. Cell viability was evaluated and miRNA profiling was performed on both tumor cells from ascites fluid and omental cake. Quantitative real-time PCR (RT-q-PCR) and western blots were used to evaluate expressions of miRNA-21 and miRNA-214 and associated proteins. Malignant cells in ascites showed greater cell viability when treated with carboplatin compared to omental metastasis. A significant up-regulation of miRNA-21 and miRNA-214 was observed in malignant cells of ascites compared to omental metastasis; this was confirmed by both cell viability assay and RT-q-PCR. Ours is the first report that demonstrates significant up-regulation of miRNA-21 and miRNA-214 in tumor cells from ascites of patients with EOC compared to omental metastasis. This finding has important implications for intrinsic carboplatin resistance in these patients.
引用
收藏
页码:403 / 409
页数:7
相关论文
共 30 条
[1]
Arts HJG, 1999, CLIN CANCER RES, V5, P2798
[2]
MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]
The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function [J].
Brueckner, Bodo ;
Stresemann, Carlo ;
Kuner, Ruprecht ;
Mund, Cora ;
Musch, Tanja ;
Meister, Michael ;
Sueltmann, Holger ;
Lyko, Frank .
CANCER RESEARCH, 2007, 67 (04) :1419-1423
[4]
Cancer of the ovary [J].
Cannistra, SA .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (24) :2519-2529
[5]
Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype [J].
Connolly, Erin ;
Melegari, Margherita ;
Landgraf, Pablo ;
Tchaikovskaya, Tatyana ;
Tennant, Bud C. ;
Slagle, Betty L. ;
Rogler, Leslie E. ;
Zavolan, Mihaela ;
Tuschl, Thomas ;
Rogler, Charles E. .
AMERICAN JOURNAL OF PATHOLOGY, 2008, 173 (03) :856-864
[6]
TGFβ-Stimulated MicroRNA-21 Utilizes PTEN to Orchestrate AKT/mTORC1 Signaling for Mesangial Cell Hypertrophy and Matrix Expansion [J].
Dey, Nirmalya ;
Ghosh-Choudhury, Nandini ;
Kasinath, Balakuntalam S. ;
Choudhury, Goutam Ghosh .
PLOS ONE, 2012, 7 (08)
[7]
Efficacy of anti-death receptor 5 (DR5) antibody (TRA-8) against primary human ovarian carcinoma using a novel ex vivo tissue slice model [J].
Estes, Jacob M. ;
Oliver, Patsy G. ;
Straughn, J. Michael, Jr. ;
Zhou, Tong ;
Wang, Wenquan ;
Grizzle, William E. ;
Alvarez, Ronald D. ;
Stockard, Cecil R. ;
LoBuglio, Albert F. ;
Buchsbaum, Donald J. .
GYNECOLOGIC ONCOLOGY, 2007, 105 (02) :291-298
[8]
Effect of TRA-8 Anti-Death Receptor 5 Antibody in Combination With Chemotherapy in an Ex Vivo Human Ovarian Cancer Model [J].
Frederick, Peter J. ;
Kendrick, James E. ;
Straughn, J. Michael, Jr. ;
Della Manna, Debbie L. ;
Oliver, Patsy G. ;
Lin, Hui-Yi ;
Grizzle, William E. ;
Stockard, Cecil R. ;
Alvarez, Ronald D. ;
Zhou, Tong ;
LoBuglio, Albert F. ;
Buchsbaum, Donald J. .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2009, 19 (05) :814-819
[9]
MiRNA-21 A biomarker predictive for platinum-based adjuvant chemotherapy response in patients with non-small cell lung cancer [J].
Gao, Wen ;
Lu, Xiao ;
Liu, Lingxiang ;
Xu, Jing ;
Feng, Dongjie ;
Shu, Yongqian .
CANCER BIOLOGY & THERAPY, 2012, 13 (05) :330-340
[10]
Evaluation of chemoresistance markers in women with epithelial ovarian carcinoma [J].
Goff, BA ;
Paley, PJ ;
Greer, BE ;
Gown, AM .
GYNECOLOGIC ONCOLOGY, 2001, 81 (01) :18-24