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MiR-21-5p enhances the progression and paclitaxel resistance in drug-resistant breast cancer cell lines by targeting PDCD4.

Authors
  • Tao, L1
  • Wu, Y Q1
  • Zhang, S P2
  • 1 Department of Breast Surgery, Chifeng Municipal Hospital, Chifeng, China. , (China)
  • 2 Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. , (China)
Type
Published Article
Journal
Neoplasma
Publication Date
Sep 01, 2019
Volume
66
Issue
5
Pages
746–755
Identifiers
DOI: 10.4149/neo_2018_181207N930
PMID: 31169019
Source
Medline
Language
English
License
Unknown

Abstract

MiR-21-5p has been identified as an oncogene to enhance human tumor progression. Here, we explored the mechanism by which miR-21-5p regulated the progression and paclitaxel (PTX) resistance in drug-resistant breast cancer (BC) cell lines. qRT-PCR assays were used to assess the expression levels of miR-21-5p and PDCD4 mRNA, and western blotting was used to detect PDCD4 protein level in PTX-resistant BC cell lines. Dual-luciferase reporter assay was used to observe the interaction between miR-21-5p and PDCD4 in PTX-resistant BC cell lines. Cell proliferation ability and IC50 values of PTX were measured by CCK-8 assay, cell cycle progression and apoptosis were determined with flow cytometry analysis, and cell migration and invasion capacities were analyzed using Transwell assay. Xenograft mice assay was used to validate the important role of miR-21-5p as a regulator on PTX-resistance BC cells growth in vivo. Then, we found that miR-21-5p was upregulated and PDCD4 was downregulated in BC tissues and PTX-resistant BC cell lines. MiR-21-5p silencing or PDCD4 overexpression ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines. Moreover, PDCD4 was demonstrated to be a direct target of miR-21-5p. MiR-21-5p exerted its regulatory effect by PDCD4 in PTX-resistant BC cell lines. Additionally, miR-21-5p silencing inhibited tumor growth in vivo. Therefore, our study demonstrated that miR-21-5p silencing ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines at least partly by targeting PDCD4, providing miR-21-5p as an effective therapeutic target for PTX-resistant BC treatment.

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