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Tumor Biology

, Volume 37, Issue 11, pp 14733–14743 | Cite as

Long non-coding RNA UCA1 enhances tamoxifen resistance in breast cancer cells through a miR-18a-HIF1α feedback regulatory loop

  • Xiunan Li
  • Yumei WuEmail author
  • Aihui Liu
  • Xin Tang
Original Article

Abstract

Recent studies reported that long non-coding RNAs (lncRNAs) might play critical roles in regulating endocrine resistance of breast cancer. Urothelial carcinoma-associated 1 (UCA1) is an lncRNA with an oncogenic role in breast cancer. This study aimed to investigate whether UCA1 is involved in acquired tamoxifen resistance in estrogen receptor (ER)-positive cancer cells. Our findings reveal that tamoxifen induces UCA1 upregulation in ER-positive breast cancer cells in a HIF1α-dependent manner. UCA1 upregulation results in significantly enhanced tamoxifen resistance. The upregulated UCA1 sponges miR-18a, which is a negative regulator of HIF1α. Therefore, UCA1 upregulation is further enhanced through a miR-18a-HIF1α feedback loop. In addition, our data also showed that miR-18a is a modulator of tamoxifen sensitivity due to its regulative effect on cell cycle proteins. miR-18a inhibitor reduced the sensitivity of MCF-7 cells to tamoxifen, while miR-18a mimics sensitized BT474 cells to tamoxifen. Therefore, miR-18a downregulation also partly contributes to acquired tamoxifen resistance in the cancer cells. These findings provide some useful information for future clinical treatment of tamoxifen resistance.

Keywords

Breast cancer UCA1 miR-18a Endocrine resistance HIF1α 

Notes

Acknowledgments

This study was supported by Beijing Natural Science Foundation (7142055.)

Compliance with ethical standards

Conflicts of interest

None.

Supplementary material

13277_2016_5348_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Breast Surgery, Beijing Obstetrics and Gynecology HospitalCapital Medical UniversityBeijingChina
  2. 2.Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology HospitalCapital Medical UniversityBeijingChina

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