NT21MP negatively regulates paclitaxel-resistant cells by targeting miR‑155‑3p and miR‑155-5p via the CXCR4 pathway in breast cancer

Wang,Yueyue; Yan,Lei; Zhang,Lingyu; Xu,Henan; Chen,Tiantian; Li,Yu; Wang,Haifeng; Chen,Sulian; Wang,Wenrui; Chen,Changjie; Yang,Qingling

doi:10.3892/ijo.2018.4477

NT21MP negatively regulates paclitaxel-resistant cells by targeting miR‑155‑3p and miR‑155-5p via the CXCR4 pathway in breast cancer

Authors:
- Yueyue Wang
- Lei Yan
- Lingyu Zhang
- Henan Xu
- Tiantian Chen
- Yu Li
- Haifeng Wang
- Sulian Chen
- Wenrui Wang
- Changjie Chen
- Qingling Yang
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Affiliations: Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China, Department of Biotechnology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China, Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China
Published online on: July 9, 2018 https://doi.org/10.3892/ijo.2018.4477
Pages: 1043-1054
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Evidence has shown that microRNAs (miRNAs) are vital in cell growth, migration, and invasion by inhibiting their target genes. A previous study demonstrated that miRNA (miR)-155‑3p and miR‑155-5p exerted opposite effects on cell proliferation, apoptosis, migration and invasion in breast cancer cell lines. An miRNA microarray was used to show that miR‑155‑3p was downregulated whereas miR‑155-5p was upregulated in paclitaxel-resistant (PR) cells compared with parental breast cancer cells. However, the role of miR‑155 in breast cancer cell invasion and metastasis remains to be elucidated. A 21-residue peptide derived from the viral macrophage inﬂammatory protein II (NT21MP), competes with the ligand of CXC chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1α, inducing cell apoptosis in breast cancer. The present study aimed to identify the underlying mechanism of action of miR‑155‑3p/5p and NT21MP in PR breast cancer cells. Quantitative polymerase chain reaction, western blotting, wound-healing, cell cycle and apoptosis assays, and Cell Counting kit-8 assay were used to achieve this goal. The combined overexpression of miR‑155‑3p with NT21MP decreased the migration and invasion ability and increased the number of apoptotic and arrested cells in the G0/G1 phase transition in vitro. The knockdown of miR‑155-5p combined with NT21MP had a similar effect on PR breast cancer cells. Furthermore, the ectopic expression of their target gene myeloid differentiation primary response gene 88 (MYD88) or tumor protein 53-induced nuclear protein 1 (TP53INP1) combined with NT21MP enhanced the sensitivity of the breast cancer cells to paclitaxel. Taken together, these findings suggested that miR‑155‑3p/5p and their target genes MYD88 and TP53INP1 may serve as novel biomarkers for NT21MP therapy through the CXCR4 pathway for improving sensitivity to paclitaxel in breast cancer.

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