期刊
BIOCHEMISTRY-MOSCOW
卷 83, 期 5, 页码 603-611出版社
MAIK NAUKA/INTERPERIODICA/SPRINGER
DOI: 10.1134/S0006297918050139
关键词
tamoxifen resistance; estrogen receptor; breast cancer; LINC00894-002; miR-200-TGF-beta 2-ZEB1
资金
- National Natural Science Foundation of China [31471226, 91440108]
- Fundamental Research Funds for The Central Universities [WK2070000044, WK2070000034]
Tamoxifen is a widely used personalized medicine for estrogen receptor (ER)-positive breast cancer, but approximately 30% of patients receiving the treatment relapse due to tamoxifen resistance (TamR). Recently, several reports have linked lncRNAs to cancer drug resistance. However, the role of lncRNAs in TamR is unclear. To identify TamR-related lncRNAs, we first used a bioinformatic approach to predict whether they have connection with known TamR-associated genes by starBase v2.0 and divided them into two groups. Group A contains lncRNAs that connect with known TamR genes and group B contains lncRNAs that show no predicted interaction. Among the 12 lncRNAs in group A, 58.3% of them are either up- or downregulated in MCF-7/TamR cells compared to the sensitive cells. In contrast, the expression levels of all group B lncRNAs are not changed in MCF-7/TamR cells. LINC00894-002 exhibits the most sophisticated network pattern and is the most downregulated lncRNA in MCF-7/TamR cells. Moreover, we find that LINC00894-002 is directly upregulated by ER alpha. Knocking down LINC00894-002 downregulates expression of miR-200a-3p and miR-200b-3p, upregulates the expression of TGF-beta 2 and ZEB1, and finally contributes to TamR. Herein, we report the first case of an inhibitory lncRNA against TamR through the miR-200-TGF-beta 2-ZEB1 signaling pathway.
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