Involvement of miR-30c in resistance to doxorubicin by
regulating YWHAZ in breast cancer cells |
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Authors: | Y Fang H Shen Y Cao H Li R Qin Q Chen L Long XL Zhu CJ Xie WL Xu |
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Institution: | 1.Department of Central Laboratory, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu, China;2.Department of Oncology, The First Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu, China;3.Department of Central Laboratory, The Fourth Affiliated People’s Hospital, Jiangsu University, Zhenjiang, Jiangsu, China |
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Abstract: | MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated
in cancer, which play crucial roles in diverse biological processes, such as
development, differentiation, apoptosis, and proliferation. The aim of this study was
to investigate whether miR-30c mediated the resistance of breast cancer cells to the
chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine
3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c
was downregulated in the doxorubicin-resistant human breast cancer cell lines
MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell
lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic
significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover,
the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase
reporter assay, and further studies indicated that the mechanism for miR-30c on the
sensitivity of breast cancer cells involved YWHAZ and its downstream p38
mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided
evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by
regulating YWHAZ in the breast cancer cell line MCF-7/ADR. |
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Keywords: | Breast cancer cells miR-30c YWHAZ Doxorubicin resistance |
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