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Erschienen in: Cancer Chemotherapy and Pharmacology 2/2019

15.11.2018 | Original Article

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

verfasst von: Shuqi Chi, Yan Liu, Xing Zhou, Dilu Feng, Xianjin Xiao, Wenliang Li, Yingchao Zhao, Hongbo Wang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2019

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
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Metadaten
Titel
Knockdown of long non-coding HOTAIR enhances the sensitivity to progesterone in endometrial cancer by epigenetic regulation of progesterone receptor isoform B
verfasst von
Shuqi Chi
Yan Liu
Xing Zhou
Dilu Feng
Xianjin Xiao
Wenliang Li
Yingchao Zhao
Hongbo Wang
Publikationsdatum
15.11.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 2/2019
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3727-0

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