LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression
Yotova I, Proestling K, Pauler F, Rainer L, Kaup L, Heine J, Sandrieser L, Wenzl R, Hudson QJ. 2025. LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression. Reproductive Biomedicine Online. 51(3), 104942.
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Journal Article
| Published
| English
Scopus indexed
Author
Yotova, Iveta;
Proestling, Katharina;
Pauler, FlorianISTA
;
Rainer, Lisa;
Kaup, Leonie;
Heine, Jana;
Sandrieser, Lejla;
Wenzl, René;
Hudson, Quanah J.

Department
Abstract
Research question: Is LINC01638 involved in regulation of epithelial-to-mesenchymal transition (EMT) in endometriosis?
Design: A prospective patient cohort study was combined with functional experiments in the 12Z endometriosis epithelial cell line to investigate the role of LINC01638 in endometriosis. Eutopic endometrial samples were collected by curettage, and ectopic endometrial lesion samples were collected by laparoscopic surgery from 24 control patients and 41 patients with endometriosis. The phenotype of 12Z cells was assessed following LINC01638 knockdown using siRNA, performing proliferation, adhesion, migration and invasion assays, as well as assessing apoptosis and cell cycle changes with flow cytometry assays. In order to assess the relationship between LINC01638 and histone deacetylase class 1 enzyme (HDAC1), LINC01638 knockdown was combined with HDAC inhibition with the specific HDAC inhibitor romidepsin.
Results: LINC01638 was up-regulated in the epithelial layer of endometriotic lesions, and LINC01638 knockdown in 12Z cells led to reduced proliferation, adhesion, migration and invasion. The reduction in proliferation was associated with increased p21 and p27 expression, and G1 phase arrest. Further analysis of LINC01638 control and knockdown cells revealed that a number of transcription factors associated with EMT are down-regulated in knockdown cells, along with the cytoskeleton regulatory gene RHOB, while HDAC1 was up-regulated. Chromatin immunoprecipitation analysis and HDAC1 inhibitory treatment combined with LINC01638 knockdown indicated that LINC01638 regulates RHOB expression via HDAC1-mediated promoter deacetylation. RHOB is up-regulated in the epithelial layer of endometriotic lesions compared with eutopic endometrium, supporting a role in the disease.
Conclusions: LINC01638 is an epigenetic regulator of the pathogenesis of endometriosis, promoting proliferation and EMT of endometriotic lesions.
Publishing Year
Date Published
2025-07-17
Journal Title
Reproductive Biomedicine Online
Publisher
Elsevier
Acknowledgement
The authors wish to thank all the participants and health professionals involved in this study. In addition, the authors wish to thank technical assistants Barbara Widmar, Matthias Witzmann-Stern and Isabella Haslinger for their work assisting with this study; and Simon Hippenmeyer for access to bioinformatic infrastructure and resources.
Open access funding was provided by the Medical University of Vienna.
Volume
51
Issue
3
Article Number
104942
ISSN
eISSN
IST-REx-ID
Cite this
Yotova I, Proestling K, Pauler F, et al. LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression. Reproductive Biomedicine Online. 2025;51(3). doi:10.1016/j.rbmo.2025.104942
Yotova, I., Proestling, K., Pauler, F., Rainer, L., Kaup, L., Heine, J., … Hudson, Q. J. (2025). LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression. Reproductive Biomedicine Online. Elsevier. https://doi.org/10.1016/j.rbmo.2025.104942
Yotova, Iveta, Katharina Proestling, Florian Pauler, Lisa Rainer, Leonie Kaup, Jana Heine, Lejla Sandrieser, René Wenzl, and Quanah J. Hudson. “LINC01638 Promotes Epithelial-to-Mesenchymal Transition in Endometriosis Epithelial Cells by up-Regulating RHOB via HDAC1 Suppression.” Reproductive Biomedicine Online. Elsevier, 2025. https://doi.org/10.1016/j.rbmo.2025.104942.
I. Yotova et al., “LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression,” Reproductive Biomedicine Online, vol. 51, no. 3. Elsevier, 2025.
Yotova I, Proestling K, Pauler F, Rainer L, Kaup L, Heine J, Sandrieser L, Wenzl R, Hudson QJ. 2025. LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression. Reproductive Biomedicine Online. 51(3), 104942.
Yotova, Iveta, et al. “LINC01638 Promotes Epithelial-to-Mesenchymal Transition in Endometriosis Epithelial Cells by up-Regulating RHOB via HDAC1 Suppression.” Reproductive Biomedicine Online, vol. 51, no. 3, 104942, Elsevier, 2025, doi:10.1016/j.rbmo.2025.104942.
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