Abstract:
BACKGROUND:The importance of individual microRNAs (miRNAs) in tumor has been established in different cancers. However, their association with tumor chemoresistance has not been fully understood. Previously, we found two novel MDR-associated microRNAs (miRNAs). In this report, we investigated the combined effects of miRNA gene cluster in chemoresistance of breast cancer. METHODS:This study was performed in two different breast cancer cell lines (MCF-7 and MCF-7/ADR). The levels of miRNAs and mRNA expression were determined by using Quantitative Real-Time PCR. Western blotting was used to detect the levels of protein molecules. Cell viability was assessed by MTS assay. Bioinformatics and Luciferase reporter assay was performed to examine miRNA binding to the 3'-UTR of target genes. RESULTS:The miR-302S family including miR-302a, miR-302b, miR-302c, and miR-302d was significantly down-regulated in P-glycoprotein (P-gp)-overexpressing MCF-7/ADR cells. Overexpression of miR-302 increased intracellular accumulation of ADR and sensitized breast cancer cells to ADR. Most importantly, miR-302S produced stronger effects than each individual member alone. The four miRNAs cooperatively downregulate P-gp expression in regulating drug sensitivity. However, our results showed that the suppression of P-gp expression by miR-302 is not through typical miRNA-mediated mRNA degradation but at the level of protein and transcription. Further studies identified MAP/ERK kinase kinase 1 (MEKK1) as a direct and functional target of miR-302. miR-302 showed combinatorial effects on MKEE1 repression and MEKK1-mediated ERK pathway. The suppression of P-gp by miR-302 was reversed by MEKK1 overexpression. CONCLUSION:Our results indicate that miR-302 cooperatively sensitizes breast cancer cells to adriamycin via suppressing P-glycoprotein by targeting MEKK1 of ERK pathway. miR-302 gene cluster may be a potential target for reversing P-gp-mediated chemoresistance in breast cancer.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Zhao L,Wang Y,Jiang L,He M,Bai X,Yu L,Wei Mdoi
10.1186/s13046-016-0300-8subject
Has Abstractpub_date
2016-02-03 00:00:00pages
25eissn
0392-9078issn
1756-9966pii
10.1186/s13046-016-0300-8journal_volume
35pub_type
杂志文章abstract::This study is aimed at evaluating the inhibitory effects of the association of hematoporphyrin and ultrasound at variable intensities with a fixed frequency of 1.1MHz in tumor nodules. Specifically, the effects were studied both in solid and ascitic S180 tumors transplanted in mice by clinical, cytochemical and ultras...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,收录出版
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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doi:10.1186/s13046-017-0614-1
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
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doi:
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 历史文章,杂志文章
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journal_title:Journal of experimental & clinical cancer research : CR
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doi:10.1186/s13046-019-1112-4
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
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journal_title:Journal of experimental & clinical cancer research : CR
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0918-9
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journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0773-8
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