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MicroRNA-34b expression enhances chemosensitivity of endometrial cancer cells to paclitaxel

ABSTRACT: 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. MYC and MET, 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 and MET are 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.

SUBMITTER: Yanokura M

PROVIDER: S-EPMC7549539 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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LncRNA RBAT1 reduces chemosensitivity of cancer cells to carboplatin/paclitaxel by sponging miR‑27b in endometrial carcinoma.

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| S-EPMC10375650 | biostudies-literature

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| S-EPMC6358874 | biostudies-literature

Inhibition of Hec1 expression enhances the sensitivity of human ovarian cancer cells to paclitaxel.

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| S-EPMC7226198 | biostudies-literature

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