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Long non-coding RNA steroid receptor activator promotes the progression of endometrial cancer via Wnt/ β-catenin signaling pathway

Authors
 Sun-Ae Park  ;  Lee Kyung Kim  ;  Young Tae Kim  ;  Tae-Hwe Heo  ;  Hee Jung Kim 
Citation
 INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, Vol.16(1) : 99-115, 2020 
Journal Title
 INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 
Issue Date
2020
Keywords
Endometrial cancer (EC) ; Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4E-BP1) ; Signaling pathway ; Steroid Receptor Activator (SRA) ; Wnt/ β-catenin signaling
Abstract
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.
Files in This Item:
T202000125.pdf Download
DOI
10.7150/ijbs.35643
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Tae(김영태) ORCID logo https://orcid.org/0000-0002-7347-1052
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174903
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