Abstract | BACKGROUND: METHODS:
MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. RESULTS: Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay. CONCLUSION: MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.
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Authors | J H Huh, T H Kim, K Kim, J-A Song, Y J Jung, J-Y Jeong, M J Lee, Y K Kim, D H Lee, H J An |
Journal | British journal of cancer
(Br J Cancer)
Vol. 109
Issue 2
Pg. 452-61
(Jul 23 2013)
ISSN: 1532-1827 [Electronic] England |
PMID | 23807165
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- MIRN106 microRNA, human
- MIRN591 microRNA, human
- MicroRNAs
- Paclitaxel
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Topics |
- Antineoplastic Agents, Phytogenic
(therapeutic use)
- Cell Line, Tumor
- Cluster Analysis
- Cystadenocarcinoma, Serous
(drug therapy, genetics, mortality)
- Drug Resistance, Neoplasm
(genetics)
- Female
- Gene Expression Regulation, Neoplastic
(physiology)
- Humans
- MicroRNAs
(genetics, physiology)
- Microarray Analysis
- Ovarian Neoplasms
(drug therapy, genetics, mortality)
- Paclitaxel
(therapeutic use)
- Survival Analysis
- Transcriptome
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