期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 57, 期 5, 页码 1145-1156出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2020.5127
关键词
endometrial cancer; microRNA; microRNA-34b; chemosensitivity; paclitaxel
类别
资金
- JSPS KAKENHI [15K10727, 16K11154]
- Grants-in-Aid for Scientific Research [16K11154, 15K10727] Funding Source: KAKEN
Aberrant DNA methylation is widely observed in various types of cancer, and expression of microRNAs (miRNAs/miRs) is suppressed by DNA methylation. The present study explored tumor suppressor miRNAs downregulated by DNA methylation in endometrial cancer cells, as the basis of a novel therapeutic approach for endometrial cancer. Among 821 candidate miRNAs, miR-34b was identified as an upregulated miRNA after demethylation treatment in all four endometrial cancer cell lines (HEC-108, SNG-II, Ishikawa and HHUA) examined. miR-34b expression with or without demethylation treatment in cancer cells was confirmed by TaqMan quantitative PCR.MYCandMET, the predicted target genes of miR-34b, were downregulated at both the RNA and protein levels following miR-34b overexpression. Following miR-34b treatment, inhibition of cell growth and invasion, and cell cycle arrest were observed in HEC-108 cells. Sensitivity to paclitaxel was increased in cancer cells with miR-34b overexpression, compared with untreated cancer cells, but this difference was not identified for cisplatin or doxorubicin.In vivo, combination treatment with miR-34b and paclitaxel markedly reduced tumor growth compared with treatment with negative control miRNA and paclitaxel. These data suggest that miR-34b enhances paclitaxel sensitivity in endometrial cancer cells, and that miR-34b andMETare key targets for treatment of endometrial cancer. The present results may contribute to the development of combination treatment with a demethylation agent, miR-34b mimic or MET inhibitor and an anticancer drug.
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