Knockdown of long non-coding HOTAIR enhances the sensitivity to progesterone in endometrial cancer by epigenetic regulation of progesterone receptor isoform B

  • Shuqi Chi
  • Yan Liu
  • Xing Zhou
  • Dilu Feng
  • Xianjin Xiao
  • Wenliang Li
  • Yingchao Zhao
  • Hongbo Wang
Original Article



Progesterone, particularly medroxyprogesterone acetate (MPA) has been mainly used for young endometrial carcinoma (EC) patients with conservative treatment. However, its treatment benefits are limited by insensitivity or acquired resistance. In this study, we aim to investigate the effect of long non-coding RNA HOTAIR on progesterone sensitivity in endometrial cancer, as well as the underlying mechanisms.


The expression of HOTAIR was detected by quantitative real-time PCR. The impact of MPA on the endometrial cancer cells was examined by MTT, colony formation, apoptosis-related protein detection and flow cytometry. Chromatin immunoprecipitation (ChIP) assay was performed to detect the regulatory mechanism between HOTAIR and progesterone receptor B (PRB). We further confirm the function of HOTAIR in vivo though xenograft tumor assay.


We found that HOTAIR inversely correlated with PRB expression in endometrial carcinoma. Knockdown of HOTAIR promoted the MPA sensitivity by upregulating PRB, which can be largely reversed by PRB downregulation. Moreover, inhibiting LSD1, a HOTAIR-associated protein that removed activating H3K4me2 chromatin marks, induced PRB expression and promoted apoptosis induced by MPA. We further showed that silencing HOTAIR strengthened the H3K4me2 occupation on the promotor of PRB.


Our findings provide compelling evidence that HOTAIR and LSD1 collaboratively repress PRB expression and thus mediate progesterone sensitivity in endometrial carcinoma cells. HOTAIR is a potential predictor for progesterone response in EC and down-regulated expression of HOTAIR might be an effective strategy for overcoming progesterone resistance.


Endometrial cancer HOTAIR Progesterone sensitivity Epigenetic modification 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants and animals were in accordance with the ethical standards of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

280_2018_3727_MOESM1_ESM.docx (396 kb)
Supplementary material 1 (DOCX 395 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Shuqi Chi
    • 1
  • Yan Liu
    • 1
  • Xing Zhou
    • 1
  • Dilu Feng
    • 1
  • Xianjin Xiao
    • 4
  • Wenliang Li
    • 3
  • Yingchao Zhao
    • 2
  • Hongbo Wang
    • 1
  1. 1.Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Cancer Center, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Texas Therapeutics Institute, Brown Foundation Institute of Molecular MedicineUniversity of Texas Health Science Center at HoustonHoustonUSA
  4. 4.Centre of Reproductive Medicine/Family Planning Research Institute, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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