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Downregulation of LINC00894-002 Contributes to Tamoxifen Resistance by Enhancing the TGF-β Signaling Pathway

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Abstract

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 ERα. Knocking down LINC00894-002 downregulates expression of miR-200a-3p and miR-200b-3p, upregulates the expression of TGF-β2 and ZEB1, and finally contributes to TamR. Herein, we report the first case of an inhibitory lncRNA against TamR through the miR-200-TGF-β2-ZEB1 signaling pathway.

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Abbreviations

ASO:

antisense oligonucleotide

ChIP:

chromatin immunoprecipitation

ER:

estrogen receptor

lncRNAs:

long noncoding RNAs

SRB:

sulforhodamine B

TamR:

tamoxifen resistance

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, School of Life Sciences, University of Science and Technology of China, 230026, Hefei, China

    Xiulei Zhang, Huihui Sun, Tao Zhu & Xiangting Wang

  2. College of Liren, Yanshan University, 066004, Qinhuangdao, China

    Meiting Wang

  3. Department of Neurobiology and Biophysics, School of Life Sciences, University of Science and Technology of China, 230026, Hefei, China

    Meiting Wang

  4. CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 230026, Hefei, China

    Xiangting Wang

Authors
  1. Xiulei Zhang
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  2. Meiting Wang
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  4. Tao Zhu
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  5. Xiangting Wang
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Correspondence to Xiangting Wang.

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Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM17-408, February 19, 2018.

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Zhang, X., Wang, M., Sun, H. et al. Downregulation of LINC00894-002 Contributes to Tamoxifen Resistance by Enhancing the TGF-β Signaling Pathway. Biochemistry Moscow 83, 603–611 (2018). https://doi.org/10.1134/S0006297918050139

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  • DOI: https://doi.org/10.1134/S0006297918050139

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