Rationale: Steroid receptor activator (SRA), a long non-coding RNA, serves as a critical regulator of gynecologic cancer. The objective of this study was to determine biological function and clinical significance of SRA expression in endometrial cancer. Method: We investigated whether SRA was involved in the development of endometrial cancer via binding to eukaryotic translation initiation factor 4E-binding protein 1 (EIF4E-BP1) as a transcription factor to enhance Wnt/ β-catenin signaling pathway. Results: Expression levels of SRA were upregulated in endometrial cancer tissues compared to those in adjacent control tissues. We also found high expression of SRA in EC cells. The relationship between SRA and EIF4E-BP1 was corroborated by transfection of a luciferase reporter plasmid. In addition, SRA knockdown inhibited the expression of EIF4E-BP1 known to play a critical role in the control of protein synthesis, cell growth, and cell survival, thus promoting tumourigenesis and epithelial-mesenchymal transition (EMT) important for cell motility and metastasis. Consistently, immunostaining and western blotting analysis showed that expression levels of β-catenin and 4EBP1 in the nucleus were significantly decreased by SRA knockdown but increased by SRA over-expression. Conclusions: These results suggest that SRA is involved in proliferation, migration, and invasion of endometrial cancer cells by increasing the expression of EIF4E-BP1 and activity of Wnt/ β-catenin signaling. These findings indicate that SRA might be a novel biomarker for predicting recurrence and prognosis. It might also serve as a promising therapeutic target in endometrial cancer.
|Number of pages||17|
|Journal||International Journal of Biological Sciences|
|Publication status||Published - 2020|
Bibliographical noteFunding Information:
This work was funded by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant no. HI17C0321) and by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (grant nos. NRF-2018R1D1A1B07049578, 2018R1A6A1A03025108 and NRF-2018R1D1A1B07049780) and by the Research Fund 2019 of the Catholic University of Korea, and BK21PLUS grant of NRF funded by the Korean government (ME) (22A20130012250).
© The author(s).
All Science Journal Classification (ASJC) codes
- Ecology, Evolution, Behavior and Systematics
- Applied Microbiology and Biotechnology
- Molecular Biology
- Developmental Biology
- Cell Biology