Dataset Information

MiR-519d-5p modulates the sensitivity of breast cancer to chemotherapy by forming a negative feedback loop with RELA.

ABSTRACT:

Background

The chemoresistance of breast cancer (BC) has become the main cause of treatment failure. MicroRNAs (miRNAs) play a critical role in tumorigenesis, development, and chemoresistance, but the underlying mechanism of miR-519d in BC development and chemotherapy sensitivity remains to be elucidated.

Methods

The levels of miR-519d-5p in BC samples and cell lines were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell viability was monitored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The in vivo effect of miR-519d-5p on tumor formation and doxorubicin response were investigated in a xenograft study. Bioinformatic analysis, luciferase reporter assay, RT-qPCR, and western blotting were conducted to validate RELA as a target gene of miR-519d-5p. We performed RT-qPCR, western blotting, chromatin immunoprecipitation (ChIP), and DNA pull down to verify miR-519d-5p as a transcriptional target of RELA.

Results

This study found that miR-519d-5p was expressed at lower levels in BC cells and tissues, and overexpression of miR-519d-5p sensitized BC to chemotherapy both in vitro and in vivo. Meanwhile, the expression of RELA was negatively correlated with miR-519d-5p. We then showed that RELA is one of the targets of miR-519d-5p: miR-519d-5p inhibited RELA expression by directly binding to its 3'-unstranslated region (3'-UTR). Conversely, it was verified that miR-519d-5p is one of the targets of transcription factor RELA, and RELA repressed miR-519d-5p by binding to the promoter region of miR-519d-5p, which forms a feedback loop.

Conclusions

Overall, the results provide a novel therapeutic strategy for the combinational use of miR-519d-5p and chemotherapeutic agents to overcome chemo-resistance by forming a negative feedback loop with RELA.

SUBMITTER: Li D

PROVIDER: S-EPMC8350717 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

MiR-519d-5p modulates the sensitivity of breast cancer to chemotherapy by forming a negative feedback loop with RELA.

Li Ding D Wang Tingting T Yu Zelei Z Zhang Yi Y Wu Xuan X Zheng Ning N Zhang Wenzhou W Wu Lixian L

Annals of translational medicine 20210701 14

<h4>Background</h4>The chemoresistance of breast cancer (BC) has become the main cause of treatment failure. MicroRNAs (miRNAs) play a critical role in tumorigenesis, development, and chemoresistance, but the underlying mechanism of miR-519d in BC development and chemotherapy sensitivity remains to be elucidated.<h4>Methods</h4>The levels of miR-519d-5p in BC samples and cell lines were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Cell viability was monitor ...[more]

PMID: 34430612

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Dataset Information

MiR-519d-5p modulates the sensitivity of breast cancer to chemotherapy by forming a negative feedback loop with RELA.

Background

Methods

Results

Conclusions

Publications

MiR-519d-5p modulates the sensitivity of breast cancer to chemotherapy by forming a negative feedback loop with RELA.

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