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miR-520d over-expression reverses chemotherapy resistance of TNBC via inhibiting autophagy protein Beclin1 / 中国肿瘤生物治疗杂志
Chinese Journal of Cancer Biotherapy ; (6): 1062-1067, 2019.
Article in Chinese | WPRIM | ID: wpr-793226
ABSTRACT
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Objective:

To investigate the role and molecular mechanism of miR-520d in reversing the chemoresistance of triple negative breast cancer (TNBC) by regulating autophagy.

Methods:

Docetaxel (Doc) resistant cell lines MDA-MB-231/Doc and MDA-MB468/Doc were constructed by using human TNBC cell lines MDA-MB-231 and MDA-MB-468 as parental cells, and the cells were divided into blank group (parental cells), control group (drug-resistant group), and miR-520d over-expression group. The expression levels of miR-520d in cells of the blank and drug-resistant groups were detected by qPCR. The Doc-sensitivity of resistant cells over-expressing miR-520d was detected by MTT assay.After MDC staining, the generation of autophagosome in cells was observed under fluorescence microscopy; the number of miR-520d over-expressed resistant cells with positive LC3 expression was observed under confocal microscopy. The luciferase reporter gene assay was used to verify the targeting relationship between miR-520d and Beclin1. The effect of miR-520d mimics on the expression of autophagy-associated protein Beclin1, and LC3Ⅰ, LC3Ⅱ in cells was detected by WB assay.

Results:

The results of qPCR showed that the expression of miR-520d in the drug-resistant TNBC cells was significantly lower than that of normal cells (P<0.01). In drug-resistant cells over-expressing miR-520d, the Doc-sensitivity was significantly improved, while the autophagy activity was significantly reduced (all P<0.01).At the same time, luciferase experiments demonstrated that Beclin1 was a possible target molecule of miR-520d (P<0.05). WB results showed that the combination of docetaxel and miR-520d mimics reduced the LC3-II/I ratio and the expression of autophagy protein Beclin1 in drug-resistant TNBC cells (all P<0.05).

Conclusion:

The regulation of miR-520d levels may alter the expression of autophagy protein Beclin1, thereby reversing Doc chemotherapy resistance in TNBC cells.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Cancer Biotherapy Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Cancer Biotherapy Year: 2019 Type: Article