miR-1207-5p regulates the sensitivity of triple-negative breast cancer cells to Taxol treatment via the suppression of LZTS1 expression

被引:35
|
作者
Hou, Xiaoke [1 ]
Niu, Zhaofeng [1 ]
Liu, Leilei [2 ]
Guo, Qiang [1 ]
Li, Haiyang [2 ]
Yang, Xiaojun [1 ]
Zhang, Xia [3 ]
机构
[1] Yuncheng Cent Hosp, Dept Breast Surg, Yuncheng 044000, Shanxi, Peoples R China
[2] Linfen Cent Hosp, Dept Oncol 1, Linfen 041000, Shanxi, Peoples R China
[3] Linfen Peoples Hosp, Dept Oncol, Binhe West Rd, Linfen 041000, Shanxi, Peoples R China
关键词
microRNA-1207-5p; triple negative breast cancer; taxol; leucine zipper tumor suppressor gene 1; THERAPEUTIC TARGETS; DOWN-REGULATION; PROLIFERATION; CHEMOSENSITIVITY; IDENTIFICATION; MICRORNAS; PROGNOSIS; INVASION; PROMOTES; PATHWAY;
D O I
10.3892/ol.2018.9687
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Taxol-based chemotherapy is a conventional therapeutic approach for the treatment of triple-negative breast cancer (TNBC). However, the insensitivity of TNBC cells to Taxol greatly limits the anticancer effect of the drug and leads to patient mortality. The present study first evaluated the expression levels of microRNA (miR)-1207-5p in human normal breast epithelial MCF-10A cells and TNBC cell lines (MDA-MB-231, MDA-MB-436 and MDA-MB-453). The results revealed that the highest miR-1207-5p level was in MDA-MB-231, which suggested an oncogenic role of miR-1207-5p in TNBC. Therefore, MDA-MB-231 served as the present study's research model in subsequent experiments. The mRNAs that functioned as tumor suppressor factors for miR-1207-5p were then determined. Leucine zipper tumor suppressor gene 1 (LZTS1), which was predicted by TargetScan 6.2 and was supported by the results of a dual luciferase assay, was identified as a target of miR-1207-5p. AntagomiR-1207-5p increased LZTS1 mRNA and protein expressions, enhanced cell growth arrest and cell apoptosis induced by Taxol in MDA-MB-231 cells. Additionally, it was observed that, when compared with Taxol treatment, the combination of Taxol and antagomiR-1207-5p induced a sharp decrease in B-cell lymphoma 2 (Bcl-2) and phosphorylated-protein kinase B expression accompanied by an increase in the Bcl-2-associated X protein expression. Finally, miR-1207-5p expression was significantly increased, while LZTS1 expression was significantly decreased, in TNBC tissues when compared with normal adjacent tissues, and there was a negative correlation between miR-1207-5p and LZTS1 expression. In addition, there was a notable elevation in the expression of miR-1207-5p and a reduction in the expression of LZTS1 in the Taxol non-responsive TNBC tissues when compared with the Taxol-responsive TNBC tissues. The results of the present study suggested that miR-1207-5p may be a promising predictor of sensitivity towards Taxol in TNBC.
引用
收藏
页码:990 / 998
页数:9
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