Advertisement

Biochemistry (Moscow)

, Volume 83, Issue 5, pp 603–611 | Cite as

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

  • Xiulei Zhang
  • Meiting Wang
  • Huihui Sun
  • Tao Zhu
  • Xiangting WangEmail author
Article

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.

Keywords

tamoxifen resistance estrogen receptor breast cancer LINC00894-002 miR-200-TGF-β2-ZEB1 

Abbreviations

ASO

antisense oligonucleotide

ChIP

chromatin immunoprecipitation

ER

estrogen receptor

lncRNAs

long noncoding RNAs

SRB

sulforhodamine B

TamR

tamoxifen resistance

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

10541_2018_617_MOESM1_ESM.pdf (1.7 mb)
Downregulation of LINC00894-002 Contributes to Tamoxifen Resistance by Enhancing the TGF-β Signaling Pathway

References

  1. 1.
    Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., and Jemal, A. (2015) Global cancer statistics, 2012, CA Cancer J. Clin., 65, 87–108.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Criscitiello, C., Fumagalli, D., Saini, K. S., and Loi, S. (2010) Tamoxifen in early-stage estrogen receptor-positive breast cancer: overview of clinical use and molecular bio-markers for patient selection, Onco Targets Ther., 4, 1–11.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Garcia-Becerra, R., Santos, N., Diaz, L., and Camacho, J. (2012) Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance, Int. J. Mol. Sci., 14, 108–145.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Xia, H., and Hui, K. M. (2014) Mechanism of cancer drug resistance and the involvement of noncoding RNAs, Curr. Med. Chem., 21, 3029–3041.CrossRefPubMedGoogle Scholar
  5. 5.
    Manavalan, T. T., Teng, Y., Litchfield, L. M., Muluhngwi, P., Al-Rayyan, N., and Klinge, C. M. (2013) Reduced expression of miR-200 family members contributes to antiestrogen resistance in LY2 human breast cancer cells, PLoS One., 8, e62334.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Gibb, E. A., Brown, C. J., and Lam, W. L. (2011) The functional role of long non-coding RNA in human carci-nomas, Mol. Cancer, 10, 1.CrossRefGoogle Scholar
  7. 7.
    Liu, Z., Sun, M., Lu, K., Liu, J., Zhang, M., Wu, W., De, W., Wang, Z., and Wang, R. (2013) The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21 WAF1/CIP1 expression, PloS One, 8, e77293.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Xue, X., Yang, Y. A., Zhang, A., Fong, K. W., Kim, J., Song, B., Li, S., Zhao, J. C., and Yu, J. (2016) LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer, Oncogene, 35, 2746–2755.CrossRefPubMedGoogle Scholar
  9. 9.
    Godinho, M., Meijer, D., Setyono-Han, B., Dorssers, L. C., and van Agthoven, T. (2011) Characterization of BCAR4, a novel oncogene causing endocrine resistance in human breast cancer cells, J. Cell. Physiol., 226, 1741–1749.CrossRefPubMedGoogle Scholar
  10. 10.
    Li, X., Wu, Y., Liu, A., and Tang, X. (2016) Long non-cod-ing RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR-18a-HIF1alpha feedback regu-latory loop, Tumour Biol., 37, 14733–14743.CrossRefPubMedGoogle Scholar
  11. 11.
    Zhang, H. Y., Liang, F., Zhang, J. W., Wang, F., Wang, L., and Kang, X. G. (2017) Effects of long noncoding RNA–ROR on tamoxifen resistance of breast cancer cells by regulating microRNA-205, Cancer Chemother. Pharmacol., 79, 327–337.CrossRefPubMedGoogle Scholar
  12. 12.
    Caia, Y., He, J., and Zhang, D. (2016) Suppression of long non-coding RNA CCAT2 improves tamoxifen-resistant breast cancer cells’ response to tamoxifen, Mol. Biol., 50, 725–730.CrossRefGoogle Scholar
  13. 13.
    Niknafs, Y. S., Han, S., Ma, T., Speers, C., Zhang, C., Wilder-Romans, K., Iyer, M. K., Pitchiaya, S., Malik, R., Hosono, Y., Prensner, J. R., Poliakov, A., Singhal, U., Xiao, L., Kregel, S., Siebenaler, R. F., Zhao, S. G., Uhl, M., Gawronski, A., Hayes, D. F., Pierce, L. J., Cao, X., Collins, C., Backofen, R., Sahinalp, C. S., Rae, J. M., Chinnaiyan, A. M., and Feng, F. Y. (2016) The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression, Nat. Commun., 7, 12791.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Li, J. H., Liu, S., Zhou, H., Qu, L. H., and Yang, J. H. (2014) starBase v2.0: decoding miRNA–ceRNA, miRNA–ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data, Nucleic Acids Res., 42, D92–97.CrossRefPubMedGoogle Scholar
  15. 15.
    Lu, M., Ding, K., Zhang, G., Yin, M., Yao, G., Tian, H., Lian, J., Liu, L., Liang, M., Zhu, T., and Sun, F. (2015) MicroRNA-320a sensitizes tamoxifen-resistant breast can-cer cells to tamoxifen by targeting ARPP-19 and ERRgamma, Sci. Rep., 5, 8735.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Pauwels, B., Korst, A. E., de Pooter, C. M., Pattyn, G. G., Lambrechts, H. A., Baay, M. F., Lardon, F., and Vermorken, J. B. (2003) Comparison of the sulforhodamine B assay and the clonogenic assay for in vitro chemoradiation studies, Cancer Chemother. Pharmacol., 51, 221–226.PubMedGoogle Scholar
  17. 17.
    Vichai, V., and Kirtikara, K. (2006) Sulforhodamine B col-orimetric assay for cytotoxicity screening, Nat. Protoc., 1, 1112–1116.CrossRefPubMedGoogle Scholar
  18. 18.
    Volders, P.-J., Helsens, K., Wang, X., Menten, B., Martens, L., Gevaert, K., Vandesompele, J., and Mestdagh, P. (2013) LNCipedia: a database for annotated human lncRNA tran-script sequences and structures, Nucleic Acids Res., 41, D246–D251.CrossRefPubMedGoogle Scholar
  19. 19.
    Tang, Z., Li, C., Kang, B., Gao, G., Li, C., and Zhang, Z. (2017) GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses, Nucleic Acids Res., doi: 10.1093/nar/gkx247 [Epub ahead of print].Google Scholar
  20. 20.
    Dias, N., and Stein, C. (2002) Antisense oligonucleotides: basic concepts and mechanisms, Mol. Canc. Ther., 1, 347–355.Google Scholar
  21. 21.
    Li, J., Han, L., Roebuck, P., Diao, L., Liu, L., Yuan, Y., Weinstein, J. N., and Liang, H. (2015) TANRIC: an inter-active open platform to explore the function of lncRNAs in cancer, Cancer Res., 75, 3728–3737.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    MacCallum, J., Keen, J., Bartlett, J., Thompson, A., Dixon, J., and Miller, W. (1996) Changes in expression of transforming growth factor beta mRNA isoforms in patients undergoing tamoxifen therapy, Br. J. Cancer, 74, 474.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Arteaga, C. L., Koli, K. M., Dugger, T. C., and Clarke, R. (1999) Reversal of tamoxifen resistance of human breast carcinomas in vivo by neutralizing antibodies to transform-ing growth factor-β, J. Natl. Cancer Inst., 91, 46–53.CrossRefPubMedGoogle Scholar
  24. 24.
    Yuan, J-h, Yang, F., Wang, F., Ma, J-z, Guo, Y-j, Tao, Q-f, Liu, F., Pan, W., Wang, T-t, and Zhou, C-c. (2014) A long noncoding RNA activated by TGF-β promotes the inva-sion-metastasis cascade in hepatocellular carcinoma, Cancer Cell, 25, 666–681.CrossRefPubMedGoogle Scholar
  25. 25.
    Wilusz, J. E., Sunwoo, H., and Spector, D. L. (2009) Long noncoding RNAs: functional surprises from the RNA world, Genes Dev., 23, 1494–1504.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Wang, J., Ye, C., Xiong, H., Shen, Y., Lu, Y., Zhou, J., and Wang, L. (2016) Dysregulation of long non-coding RNA in breast cancer: an overview of mechanism and clinical implication, Oncotarget, 8, 5508–5522.PubMedCentralGoogle Scholar
  27. 27.
    Buck, M. B., and Knabbe, C. (2006) TGF-beta signaling in breast cancer, Ann. N. Y. Acad. Sci., 1089, 119–126.CrossRefPubMedGoogle Scholar
  28. 28.
    Lin, S., and Gregory, R. I. (2015) MicroRNA biogenesis pathways in cancer, Nat. Rev. Cancer, 15, 321–333.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • Xiulei Zhang
    • 1
  • Meiting Wang
    • 2
    • 3
  • Huihui Sun
    • 1
  • Tao Zhu
    • 1
  • Xiangting Wang
    • 1
    • 4
    Email author
  1. 1.Department of Cell and Developmental Biology, School of Life SciencesUniversity of Science and Technology of ChinaHefeiChina
  2. 2.College of LirenYanshan UniversityQinhuangdaoChina
  3. 3.Department of Neurobiology and Biophysics, School of Life SciencesUniversity of Science and Technology of ChinaHefeiChina
  4. 4.CAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesHefeiChina

Personalised recommendations